|List |< first << previous [record 19 of 511] next >> last >||
|Gene Name||paired box 5|
|Chromosomal Location||44,531,145-44,710,487 bp (-)|
|MGI Phenotype||Null mutants exhibit impaired development of the midbrain resulting in a reduced inferior colliculus and an altered cerebellar folial pattern, failure of B cell differentiation, runting, and high postnatal mortality with few survivors.|
|Amino Acid Change|
|Institutional Source||Beutler Lab|
Ensembl: ENSMUSP00000014174 (fasta)
|Gene Model||not available|
|Phenotypic Category||decrease in B cells, immune system, T-dependent humoral response defect- decreased antibody response to rSFV, T-independent B cell response defect- decreased TNP-specific IgM to TNP-Ficoll immunization|
|Alleles Listed at MGI|
|Mode of Inheritance||Unknown|
|Local Stock||Live Mice, Sperm|
|Last Updated||04/28/2017 6:56 PM by Katherine Timer|
|Record Created||09/14/2010 5:55 PM by Carrie N. Arnold|
|Other Mutations in This Stock||
Stock #: K2124 Run Code: SLD00303
Coding Region Coverage: 1x: 88.1% 3x: 81.9%
Validation Efficiency: 194/202
The Apple mutation was identified in a T-independent B cell response screen of N-ethyl-N-nitrosourea (ENU)-mutagenized G3 mice whereby homozygous Apple mutants had a diminshed T-independent antibody response to 4-hydroxy-3-nitrophenylacetyl-Ficoll (NP-Ficoll) (Figure 1). Homozygotes also had a diminished T-dependent antibody response to ovalbumin administered with aluminum hydroxide (Figure 2A) and recombinant Semliki Forest virus (rSFV)-encoded β-galactosidase (rSFV-β-gal), another T-dependent antigen (Figure 2B). The Apple mice exhibited a global reduction in antibody subtypes, with the exception of IgE and IgG3 (Figure 3). Fluorescence activated cell sorting (FACS) of peripheral blood from homozygous Apple mice determined that the Apple mice have a significant depletion of B cells with a corresponding increase in the percentage of T cells (including CD4+ and CD8+), macrophages, and monocytes (Figure 4).
|Nature of Mutation|
Whole genome sequencing of a homozygous Apple mouse using the SOLiD technique identified an A to T transversion at base pair 44,724,449 on Chromosome 4 in the GenBank genomic region NC_00070 encoding Pax5 (NCBI Ref37) (Figure 5). This mutation is 175 nt 5’ to the ATG.
The mutated nucleotide is indicated in red lettering and the start codon (ATG) is highlighted. This mutation results in loss of Pax5 protein expression (Figure 6).
Pax5 encodes Pax5 [alternatively, B-cell lineage-specific activator protein (BSAP)], a member of the paired box (PAX) family of transcription factors that have roles in cellular differentiation, migration, and proliferation (1-5). Pax5 has been further classified as a member of a Pax family subgroup that includes Pax2 and Pax8. The Pax5/2/8 subgroup share a highly conserved paired box DNA binding domain (PRD), an octapeptide motif, a partial homeodomain, a transactivation domain, and a repressor domain (1;6-12) (Figure 7). Pax5 recognizes target genes via the PRD, a 128 amino acid (aa) domain that has two helix-turn-helix motifs separated by a polypeptide linker (4;6;9;12-16). At the N-terminus, a β-hairpin binds to the DNA phosphate backbone, followed by a β-turn that contacts the minor groove of DNA targets (8;12;15-17). The N-terminus is also essential for the recombination function of Pax5 (see the “VH-to-DJH” subsection in the “Background”, below) (8). The polypeptide linker also contributes to DNA binding by contacting the minor groove (12). The centrally located octapeptide motif (TN8TCCT; N can be any combination of eight nucleotides) is a characteristic feature of most Pax proteins and is a region rich in proline, serine, threonine, and tyrosine residues [(18-20); reviewed in (21)]. The octapeptide motif is required for Pax5-Groucho-mediated gene repression; mutation or deletion of this sequence leads to an increase in the transactivation of Pax proteins (18-20;22). Also, the octapeptide motif has the potential to direct cytosine methylation to surrounding gene sequences (23). The partial homeodomain of Pax5 is not required for transcriptional activation of Pax5 target genes, but is required for Pax5-mediated activation of recombination, as deletion of this domain resulted in impaired RAG-mediated recombination (see the “VH-to-DJH” subsection in the “Background”, below) (8). Although the homeodomain is not required for activation of target genes, it is required for interaction with the TATA box binding protein, retinoblastoma protein, and the death domain-associated protein Daxx (24;25) as well as for the recruitment of the Groucho corepressor (18), and the cooperation of Pax5 and Ets-1 (17;26). The 55 amino acid proline-, serine-, and threonine-rich transactivation domain and repressor sequences are at the C-terminus of Pax5 (10;18). The transactivation domain is active in both promoter and enhancer positions during Pax5-mediated regulation of gene expression and can be negatively regulated by the adjacent repressor sequences at the extreme C-terminus (10;18).
E1A-binding protein (p300), a histone acetyltransferase that regulates transcription through chromatin remodeling, interacts with the Pax5 C-terminus, and can subsequently facilitate the acetylation of several lysines in the Pax5 N-terminal PRD (e.g., Lys67, Lys87, Lys94, Lys98, and Lys103) upon p300 overexpression (7). Mutations of Lys67, Lys87, Lys89, or Lys103 altered the induction of Pax5 target genes (e.g., CD19 and Blnk (B cell linker; see the record for busy)) in murine pro B cells [see Table 2 for the functional significance of these Pax5 targets; (7)], indicating that Pax5 activity is regulated through acetylation.
Pax5 generates multiple isoforms from two known alternative promoters to generate transcripts with distinct first exons (exon 1A and 1B) and otherwise similar in-frame sequences [(9;11;27-29); reviewed in (30)]. Alternative splicing also occurs throughout the transcript to generate multiple protein isoforms [(9); reviewed in (30)]. In both murine spleen and B-lymphoid cell lines, Pax5 generates four isoforms by alternative splicing that are expressed at detectable levels in normal B cells: Pax-5a (i.e., full-length Pax5), Pax5b, Pax5d, and Pax5e (28;31) (Figure 7). Pax-5d lacks exons 6-10 and Pax-5e lacks exons 2 and 6-10 (31). As a result, Pax5a and Pax5d, but not Pax5e, possess an intact DNA-binding domain; Pax5d and Pax5e do not have transactivation, repression, or partial homeodomain homology regions, but do contain a novel 128 base pair sequence with an unknown function (28;31). In a transient transfection system, the Pax5d and Pax5e isoforms worked to either compete or enhance the transactivating function of Pax5a: Pax5d had a transactivating function opposite of Pax5a, while isoform Pax5e increased the activity of Pax5a (31). Lowen et al. also showed that the ratio of Pax5d to Pax5e correlated with the proliferation state of the lipopolysaccharide-activated B cell: increased levels of Pax-5e led to increased proliferation, while increased Pax5d levels inhibited cell growth (31). The function of Pax-5b was not addressed. Some studies have indicated that the differential expression of PAX5 isoforms can be disease-specific in B cell malignancies (11;32;33). However, the findings have been inconsistent as isoform expression patterns differed between the studies, even in normal cells (11;32;33). One study showed that there were no significant differences in PAX5 transcript patterns between normal and cancerous B-lymphocytes (11). In contrast, another study showed a higher number or leukemia-specific isoforms in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) (33). Robichaud et al. identified the expression of five PAX5 isoforms that were generated through alternative splicing in the 3’ region in healthy B-lymphocytes, B cell lines, and primary lymphoma samples (9). The isoforms excluded different combinations of exons 7-9 resulting in changes at the C-terminus of the protein (i.e., shorter protein variants) (9). In three of the isoforms, there was a shift in the reading frame that resulted in novel protein sequences that contained a higher ratio of proline, serine, and threonine residues (9). In this study, all of the PAX5 isoforms could recognize and bind the same DNA targets, but with different transactivation potentials (9). Furthermore, in individual lymphoma samples, Robichaud et al. noted one predominant isoform, either the full length PAX5 or PAX5Δ8, an isoform that lacks 34 amino acids within the transactivating domain; healthy samples expressed multiple isoforms (9). This study also determined that upon activation of distinct cellular pathways with mitogenic agents, different isoform expression patterns were induced (9). In another study, on ‘aged’ normal lymphocytes, researchers found that transcripts in these lymphocytes corresponded to isoforms already described (9;11), including those with various exon deletions (e.g., Δ2, Δ7/8, Δ2/7/8, Δ2/7/8/9, Δ2/4/8, and Δ2/3/4/8) (32). Nebral et al. found that there was a time-dependent accumulation of splice variants, indicating that the conflicting finds in other studies may be due to unintentional ‘ageing’ of lymphocytes or cold shock conditions (32).
Pax5 interacts with partner proteins to increase Pax5 specificity for target genes [Table 1; (16)]. Pax5 can form ternary complexes between Pax5, Ets proto-oncogene family proteins, and DNA [Figure 8; (26)]. The crystal structure of the ternary complex of the Pax5 PRD (aa 19-142) and the Ets domain (aa 335-436) of Ets-1 bound to a 25 base pair Mb-1 DNA promoter fragment has been solved at a resolution of 2.25 Å [Figure 8; (17); PDB: 1K78]. Pax5 binds DNA similar to Pax6 [PDB: 6PAX; (14)] in that the N-terminal domain (NTD) and C-terminal domain (CTD) of the Pax5 PRD each have three α helices with a helix-turn-helix motif that contact the DNA major groove (17). Furthermore, the NTD has a short β hairpin at its N-terminus, followed by a β turn; the linker that connects the NTD and CTD binds in the DNA minor groove in an extended conformation (17). The Pax5 PRD has several direct contacts with the DNA bases as well as contacts with the sugar phosphate backbone (17). For example, in helix C (i.e., the recognition helix), His62 directly contacts G9 (and indirectly contacts T10 and A11 through water-mediated interactions) and Lys67 directly contacts T11 (17). Previous studies had determined that His62 is essential for Pax5 binding, as mutations at this base results in 95% loss in Pax5 binding (16;26). Within the β turn, Asn29 and Gly30 contact the minor groove through direct and water-mediated interactions (17). Residues Ile83, Gly84, Gly85, and Ser86 within the linker domain contact the minor groove through main chain or side chain atoms (17). Within the CTD, Arg137 is in van der Waals contact with T21 and S133 is in a hydrogen bond with G23 in the major groove (17). Pax5 recruits Ets-1 to a Pax5-Ets binding site to subsequently enhance its DNA-binding ability at the promoter of the Mb-1 (alternatively, Ig-α; see the record for crab)) gene; Gln22 in Pax5 is an essential residue for this interaction [(7;12;16;17;26;34-36); reviewed in (30)]. The interaction of Pax5 with Ets-1 counteracts Ets-1 autoinhibition to subsequently increase the binding of Ets-1 to the Mb-1 promoter >1000-fold (34). In addition to Ets-1, Pax5 can recruit other members of the Ets family (i.e., Fli-1, GABPα (together with the ankyrin-repeat protein GABPβ), and PU.1) to the Mb-1 promoter in vitro (16;37-39); reviewed in (21)]. In the case of PU.1, the interaction with Pax5 can result in either a cooperative function (e.g., recruiting Groucho proteins such as Grg4 (7;24;38)) to the Igh locus (38)), or a repressive function (e.g., antagonizing activity at the Igk locus (37)).
Pax5 is expressed in the embryonic central nervous system (transiently in the mesencephalon (i.e., the midbrain), in the midbrain-hindbrain boundary preceding the development of the midbrain and cerebellum, and spinal cord) and fetal liver, B-lymphocytes, and adult testis [(3;4;43-45); reviewed in (21;30)]. In B-lymphocytes, Pax5 expression is initiated in pre-pro-B cells and expressed by the B220+ pro-B cell stage in the bone marrow (46;47). Expression persists to the mature B cell stage in peripheral lymphoid organs where it is subsequently repressed in terminally differentiated plasma cells [(7;44;48-51); reviewed in (21;52)].
Several factors regulate Pax5 expression. For example, in adult B lymphopoiesis, the transcription factors E2A and early B cell factor (EBF1) initiate Pax5 expression [(53;54); reviewed in (55)]. Also, Pax2 activates Pax5 expression via binding to an enhancer sequence within the Pax5 gene (45). Metastasis-associated protein 1 (MTA1) has also been identified as a regulator of Pax5 transcription [(56); reviewed in (30)]. The JAK2/STAT5 pathway regulates Pax5 activity and may also regulate its expression: phosphorylated STAT5 (see record for domino for information on STAT1) enhances activation of the Pax5 promoter in pre-B cells (57). Also, JAK2 activation can induce the DNA-binding ability and nuclear localization of Pax5 in breast carcinoma cells (58).
The Pax protein family regulates pattern formation, morphogenesis, cellular differentiation, and organogenesis by activating (or repressing) genes that encode secreted proteins, cell surface receptors, cell cycle regulators, and transcription factors [(3;16); reviewed in (21)]. Pax5/BSAP was identified as a regulator of B cell lineage development (7;48;49) that also plays a role in neural development (44;50) and cancer (1;11;48). In order to facilitate gene regulation, Pax5 can either induce active chromatin (to activate target genes) or eliminate active chromatin (to repress genes) (59). Pax5 induces chromatin changes by recruiting both histone-modifying complexes and chromatin-remodeling complexes to the target genes (48;59). ChIP profiling of histone modifications in Pax5-deficient cells determined that Pax5 induces H3K4 methylation and H3K9 acetylation at regulatory elements of target genes [(59;60); reviewed in (52)]. In the case of repressed genes, Pax5 eliminates active histone modifications (59).
Pax5 and B Cells
Pax5 plays a role in several aspects of B cell biology including the initiation of B cell lineage commitment in the bone marrow, maintenance of the B cell fate in more mature cells, V-DJ recombination of the Igh locus, and B cell migration [(25;44;48;61); reviewed in (62)].
Early B cell differentiation
Mutation of Pax5 leads to B cell developmental arrest at an early progenitor B cell stage in the bone marrow [(50); Figure 9]. During B cell differentiation from a common hematopoietic stem cell progenitor to a mature B cell, Pax5 and other lineage-specific B lymphoid transcription factors such as EBF and E2A function to both activate B lineage-specific genes as well as to repress the transcription of other lineage-inappropriate genes (1;9;18;21;47-50;52;60;61;63-67). Pax5 can bind to a large part of the cis-regulatory genome (i.e., ~8000 Pax5 target genes) in pro-B and mature B cells (47). Microarray analysis of both wild-type and Pax5-deficient pro-B cells found that Pax5 repressed 110 genes and activate 170 genes (46;60;61). The Pax5-regulated genes included those that encode regulatory and structural proteins that have diverse functions such as transcriptional control, adhesion, migration, immune function, cellular metabolism, and receptor signaling [Table 2; (47;59-61;68); reviewed in (52;55).
Mature B cell function, identity, and survival
In addition to its role in early B cell lymphopoiesis, Pax5 also functions in mature B cells to downregulate B cell-specific genes and reactivate lineage-inappropriate genes (e.g., X-box-binding protein 1 (Xbp1) (71;81), B lymphocyte-induced maturation protein 1 [Blimp-1; (68;81)], immunoglobulin J chain (Igj) (82), and the Igh 3′ enhancer (83-85)) that were previously repressed during B cell maturation to maintain B cell identity throughout B lymphopoiesis (i.e., to repress the plasma cell pathway [(47;60;68;78;86); reviewed in (21)]. Pax5 also functions to control the migration of committed B cells by activating genes that code for adhesion receptors as well as adaptors and effectors downstream of integrin signaling [(59;60); reviewed in (52)]. In a study with conditional knockout of Pax5 in mature B cells, loss of Pax5 caused dedifferentiation of mature B cells into uncommitted progenitors in the bone marrow and the subsequent conversion of those progenitors to functional T cells (78;87). Figure 10 shows an overall view of BCR signaling; factors controlled by Pax5 are bolded.
In Pax5−/− progenitors, VH-DJH recombination of the distal VHJ558 gene family is reduced by ∼50-fold [(50); reviewed in (52)]. Expression of Pax5 in developing T lineage cells in vitro can induce rearrangement of DH-proximal VH7183 genes to the DJH region (85;88). In situ hybridization determined that Pax5 mediates Igh locus contraction and subsequent distal VHJ558 gene recombination (83-85). Subsequent findings determined that Pax5 binds to the VH coding regions and subsequently facilitates RAG1-RAG2 (see the records for maladaptive and snowcock, respectively)-mediated VH-to-DJH recombination by physically interacting with RAG1-RAG2 (8). Zhang et al. propose two Pax5 functions in regulating Igh recombination (8). One, Pax5 binds to the Igh enhancer regions to establish the proper chromosomal configuration for VH-to-DJH rearrangements. Two, the binding of Pax5 to VH coding regions as well as to the RAG1-RAG2 complex mediates RAG-mediated recombination of VH genes (8).
Midbrain and cerebellum development
Studies have found that the Pax5-Pax2 complex is necessary for development of the midbrain and cerebellum (89). In a mouse model in which only one copy of both Pax2 (Pax2+/-) and Pax5 (Pax5+/-) were expressed, 20% of the compound heterozygotes had missing inferior colliculi and disrupted vermis of the cerebellum (89). A compound model with ablation of Pax5 expression (Pax5-/-) and Pax2 heterozygosity had complete loss of the posterior midbrain and cerebellum by embryonic (E) day 9.5 (89). In the chick brain, changes in Pax5 expression via transfection resulted in swelling of the anterior tectum and changed the diencephalon into a tectum-like structure (90). This study proposed a role of Pax5 in regulating the activity of the isthmus organizer (90).
Pax5 in cancer
Pax5 has been proposed to act as either an oncogene (11;48) or a tumor suppressor (1;87) in human cancers. PAX5 point mutations, monallelic loss of PAX5, and PAX5 fusions with other genes that cause increased Pax5 expression [e.g., PAX5 fusion to IGH (27;91-94)] have been identified in acute lymphoblastic leukemia (ALL) cell lines (i.e., REH and a B-lymphoid cell line derived from a patient) and in lymphoplasmocytoid lymphoma [(10;95); reviewed in (52)]. Overexpression or aberrant somatic hypermutations of PAX5 has also been identified in non-Hodgkin lymphoma [(27;96;97); reviewed in (30)]. In addition to B cell-associated cancers, PAX5 deregulation has been linked to increased malignancy in nonlymphoid cancers such as astrocytomas, medulloblastomas, neuroblastomas, oral carcinomas, colorectal carcinomas, cervical carcinomas, bladder carcinomas, breast cancer, and small-cell lung carcinomas by altering cancer proliferation, apoptosis, and phenotype transitioning [(42;58); reviewed in (30)]. A recent study on hepatocellular cancer (HCC) showed that ectopic expression of PAX5 suppressed HCC growth through the induction of p53-mediated apoptosis indicating that, in the case of hepatocarcinogenesis, PAX5 functions as a tumor suppressor (1).
Pax5 animal models
Pax5 knockout (Pax5-/-) mice exhibit growth retardation and early death by three weeks of age (44). The ~5% of Pax5-/- mice to survive to adulthood were fertile, but were runted (44). Pax5-/- mice are osteopenic, are missing ~60% of their bone mass, and their spleens produced ~5 times the amount of osteoclasts compared to controls (3). Examination of the brains of Pax5-/- mice determined that the inferior colliculus in the auditory midbrain region was underdeveloped near the midline by as early as embryonic day (E) 16.5, but hearing was not affected (44;98). In the Pax5-/- mice, B cell development is arrested at the pro-B cell stage resulting in a lack of immunoglobulin in the serum [(3;25;44;50;86); reviewed in (21)]. In the Pax5-/- fetal liver, B cell development halts before the appearance of B220+ progenitors (50); in the Pax5-/- bone marrow, development progresses to a c-Kit+B220+ progenitor cell stage [(44;50); reviewed in (52)]. Pro-B cells from Pax5-/- mice can differentiate into almost all hemopoietic cell lineages both in vitro and in vivo [Figure 11; (18;67;99;100)]. Retroviral transduction of Pax5 causes the Pax5-deficient pro-B cells to progress along the B-lymphoid lineage (18;67;99). DH-to-JH rearrangement proceeds normally in the Pax5-/- mice along with rearrangement of a subset of the VH7183 genes; rearrangement of DH-distal VHJ558 genes is severely compromised (8;101).
The Apple mutation causes a loss of Pax5 protein expression that subsequently causes defects in B cell maturation. Similar to previous studies using conditional knockout or Pax5 (78;87) and the Pax5-/- mice (18;67;99;100), the loss of Pax5 expression in Apple is proposed to cause a conversion of B cell progenitors to other lymphoid cells. Similar to the Pax5-/- mice, arrest of B cell development in the Apple mice leads to a reduction in the amount of immunoglobulin in the serum [(3;25;44;50;86); reviewed in (21)]. It is possible that the mutation with the 5’ untranslated region of Pax5 results in alteration or prevention of binding of a protein (e.g., Pax2, E2A, or EBF1) that regulates Pax5 expression. Loss of this association would subsequently result in reduced protein expression.
|Primers||Primers cannot be located by automatic search.|
Apple genotyping is performed by amplifying the region containing the mutation using PCR, followed by sequencing of the amplified region to detect the single nucleotide transition.
Apple_PCR_F: 5’- TCTCCTCAAGTGAGCACACAGATCC -3’
Apple_PCR_R: 5’- ATCATTTCACGGTGCCTTCGGACG -3’
Primer for sequencing
Apple Seq_R: 5’- CGGAAGGCTTCAATTATTCCGAC -3’
The following sequence of 714 nucleotides are amplified (Chr. 4: 44710046-44710759, GRCm38; NCBI RefSeq NC_000070):
tctcctcaag tgagcacaca gatccaaact tgaacatctc cagattaaca ccaacacaag tatcagaaac agaatcaaac aaaaccaaag aaaacaggcc tccttgaaga caccttgacg gactagtgaa aaccatgtga acgcactgta gaaggacagg ccttttcctg agaaaactac acacacacac acacacacac acacacacac acacaaacac acacaccttt cttcttgcat ggatattagc atggatacta gcactgggta gtgtcccaga gtaagcatgg atgaatcccg tttcgcggtg ttcctacctg tcctgatggt ccgaggagtc gggtaatttt tctctaaatc catttcgata tttcaggact tgatgaaatg gacagcgagg aaaagtttcc actttttttg gggtgtcttt tttccttttc tttctttttt cttttctttt ttctttcttt gttttatttt cttttctccc tctttttctt tcttcctttc ctctttcttt ctttctttct ttctttcttt ctttctttct ttctttcttt ctttctttct ttcttttttt tggtgctggg gcccgctcac aagtcggaat aattgaagcc ttccgctccc ccgccgagct ggggtagctg atcactgagc tgaaactaaa cgttttaggt ggaaaaaaag cgtccgaagg caccgtgaaa tgat
Primer binding sites are underlined; sequencing primer binding sites are highlighted in gray; the mutated nucleotide is indicated in red (T>A, Chr. + strand (shown); A>T, sense strand).
1. Liu, W., Li, X., Chu, E. S., Go, M. Y., Xu, L., Zhao, G., Li, L., Dai, N., Si, J., Tao, Q., Sung, J. J., and Yu, J. (2011) Paired Box Gene 5 is a Novel Tumor Suppressor in Hepatocellular Carcinoma through Interaction with p53 Signaling Pathway. Hepatology. 53, 843-853.
2. Schafer, B. W. (1998) Emerging Roles for PAX Transcription Factors in Cancer Biology. Gen Physiol Biophys. 17, 211-224.
3. Horowitz, M. C., Xi, Y., Pflugh, D. L., Hesslein, D. G., Schatz, D. G., Lorenzo, J. A., and Bothwell, A. L. (2004) Pax5-Deficient Mice Exhibit Early Onset Osteopenia with Increased Osteoclast Progenitors. J Immunol. 173, 6583-6591.
4. Adams, B., Dorfler, P., Aguzzi, A., Kozmik, Z., Urbanek, P., Maurer-Fogy, I., and Busslinger, M. (1992) Pax-5 Encodes the Transcription Factor BSAP and is Expressed in B Lymphocytes, the Developing CNS, and Adult Testis. Genes Dev. 6, 1589-1607.
5. Bopp, D., Burri, M., Baumgartner, S., Frigerio, G., and Noll, M. (1986) Conservation of a Large Protein Domain in the Segmentation Gene Paired and in Functionally Related Genes of Drosophila. Cell. 47, 1033-1040.
6. Czerny, T., Schaffner, G., and Busslinger, M. (1993) DNA Sequence Recognition by Pax Proteins: Bipartite Structure of the Paired Domain and its Binding Site. Genes Dev. 7, 2048-2061.
7. He, T., Hong, S. Y., Huang, L., Xue, W., Yu, Z., Kwon, H., Kirk, M., Ding, S. J., Su, K., and Zhang, Z. (2011) Histone Acetyltransferase p300 Acetylates Pax5 and Strongly Enhances Pax5-Mediated Transcriptional Activity. J Biol Chem. 286, 14137-14145.
8. Zhang, Z., Espinoza, C. R., Yu, Z., Stephan, R., He, T., Williams, G. S., Burrows, P. D., Hagman, J., Feeney, A. J., and Cooper, M. D. (2006) Transcription Factor Pax5 (BSAP) Transactivates the RAG-Mediated V(H)-to-DJ(H) Rearrangement of Immunoglobulin Genes. Nat Immunol. 7, 616-624.
9. Robichaud, G. A., Nardini, M., Laflamme, M., Cuperlovic-Culf, M., and Ouellette, R. J. (2004) Human Pax-5 C-Terminal Isoforms Possess Distinct Transactivation Properties and are Differentially Modulated in Normal and Malignant B Cells. J Biol Chem. 279, 49956-49963.
10. Dorfler, P., and Busslinger, M. (1996) C-Terminal Activating and Inhibitory Domains Determine the Transactivation Potential of BSAP (Pax-5), Pax-2 and Pax-8. EMBO J. 15, 1971-1982.
11. Arseneau, J. R., Laflamme, M., Lewis, S. M., Maicas, E., and Ouellette, R. J. (2009) Multiple Isoforms of PAX5 are Expressed in both Lymphomas and Normal B-Cells. Br J Haematol. 147, 328-338.
12. Fitzsimmons, D., Lutz, R., Wheat, W., Chamberlin, H. M., and Hagman, J. (2001) Highly Conserved Amino Acids in Pax and Ets Proteins are Required for DNA Binding and Ternary Complex Assembly. Nucleic Acids Res. 29, 4154-4165.
13. Baumgartner, S., Bopp, D., Burri, M., and Noll, M. (1987) Structure of Two Genes at the Gooseberry Locus Related to the Paired Gene and their Spatial Expression during Drosophila Embryogenesis. Genes Dev. 1, 1247-1267.
14. Xu, H. E., Rould, M. A., Xu, W., Epstein, J. A., Maas, R. L., and Pabo, C. O. (1999) Crystal Structure of the Human Pax6 Paired Domain-DNA Complex Reveals Specific Roles for the Linker Region and Carboxy-Terminal Subdomain in DNA Binding. Genes Dev. 13, 1263-1275.
15. Xu, W., Rould, M. A., Jun, S., Desplan, C., and Pabo, C. O. (1995) Crystal Structure of a Paired Domain-DNA Complex at 2.5 A Resolution Reveals Structural Basis for Pax Developmental Mutations. Cell. 80, 639-650.
16. Wheat, W., Fitzsimmons, D., Lennox, H., Krautkramer, S. R., Gentile, L. N., McIntosh, L. P., and Hagman, J. (1999) The Highly Conserved Beta-Hairpin of the Paired DNA-Binding Domain is Required for Assembly of Pax-Ets Ternary Complexes. Mol Cell Biol. 19, 2231-2241.
17. Garvie, C. W., Hagman, J., and Wolberger, C. (2001) Structural Studies of Ets-1/Pax5 Complex Formation on DNA. Mol Cell. 8, 1267-1276.
18. Eberhard, D., Jimenez, G., Heavey, B., and Busslinger, M. (2000) Transcriptional Repression by Pax5 (BSAP) through Interaction with Corepressors of the Groucho Family. EMBO J. 19, 2292-2303.
20. Lechner, M. S., and Dressler, G. R. (1996) Mapping of Pax-2 Transcription Activation Domains. J Biol Chem. 271, 21088-21093.
21. Holmes, M. L., Pridans, C., and Nutt, S. L. (2008) The Regulation of the B-Cell Gene Expression Programme by Pax5. Immunol Cell Biol. 86, 47-53.
22. Burri, M., Tromvoukis, Y., Bopp, D., Frigerio, G., and Noll, M. (1989) Conservation of the Paired Domain in Metazoans and its Structure in Three Isolated Human Genes. EMBO J. 8, 1183-1190.
23. Ziman, M. R., and Kay, P. H. (1998) A Conserved TN8TCCT Motif in the Octapeptide-Encoding Region of Pax Genes which has the Potential to Direct Cytosine Methylation. Gene. 223, 303-308.
24. Eberhard, D., and Busslinger, M. (1999) The Partial Homeodomain of the Transcription Factor Pax-5 (BSAP) is an Interaction Motif for the Retinoblastoma and TATA-Binding Proteins. Cancer Res. 59, 1716s-1724s; discussion 1724s-1725s.
25. Emelyanov, A. V., Kovac, C. R., Sepulveda, M. A., and Birshtein, B. K. (2002) The Interaction of Pax5 (BSAP) with Daxx can Result in Transcriptional Activation in B Cells. J Biol Chem. 277, 11156-11164.
26. Fitzsimmons, D., Hodsdon, W., Wheat, W., Maira, S. M., Wasylyk, B., and Hagman, J. (1996) Pax-5 (BSAP) Recruits Ets Proto-Oncogene Family Proteins to Form Functional Ternary Complexes on a B-Cell-Specific Promoter. Genes Dev. 10, 2198-2211.
27. Busslinger, M., Klix, N., Pfeffer, P., Graninger, P. G., and Kozmik, Z. (1996) Deregulation of PAX-5 by Translocation of the Emu Enhancer of the IgH Locus Adjacent to Two Alternative PAX-5 Promoters in a Diffuse Large-Cell Lymphoma. Proc Natl Acad Sci U S A. 93, 6129-6134.
28. Zwollo, P., Arrieta, H., Ede, K., Molinder, K., Desiderio, S., and Pollock, R. (1997) The Pax-5 Gene is Alternatively Spliced during B-Cell Development. J Biol Chem. 272, 10160-10168.
29. Borson, N. D., Lacy, M. Q., and Wettstein, P. J. (2002) Altered mRNA Expression of Pax5 and Blimp-1 in B Cells in Multiple Myeloma. Blood. 100, 4629-4639.
30. O'Brien, P., Morin, P.,Jr, Ouellette, R. J., and Robichaud, G. A. (2011) The Pax-5 Gene: A Pluripotent Regulator of B-Cell Differentiation and Cancer Disease. Cancer Res. 71, 7345-7350.
31. Lowen, M., Scott, G., and Zwollo, P. (2001) Functional Analyses of Two Alternative Isoforms of the Transcription Factor Pax-5. J Biol Chem. 276, 42565-42574.
32. Nebral, K., Krehan, D., and Strehl, S. (2011) Expression of PAX5 Splice Variants: A Phenomenon of Stress-Induced, Illegitimate Splicing? Br J Haematol. 155, 277-280.
33. Santoro, A., Bica, M. G., Dagnino, L., Agueli, C., Salemi, D., Cannella, S., Veltroni, M., Cetica, V., Giarin, E., Fabbiano, F., Basso, G., and Arico, M. (2009) Altered mRNA Expression of PAX5 is a Common Event in Acute Lymphoblastic Leukaemia. Br J Haematol. 146, 686-689.
34. Fitzsimmons, D., Lukin, K., Lutz, R., Garvie, C. W., Wolberger, C., and Hagman, J. (2009) Highly Cooperative Recruitment of Ets-1 and Release of Autoinhibition by Pax5. J Mol Biol. 392, 452-464.
35. Maier, H., Colbert, J., Fitzsimmons, D., Clark, D. R., and Hagman, J. (2003) Activation of the Early B-Cell-Specific Mb-1 (Ig-Alpha) Gene by Pax-5 is Dependent on an Unmethylated Ets Binding Site. Mol Cell Biol. 23, 1946-1960.
36. Maier, H., Ostraat, R., Parenti, S., Fitzsimmons, D., Abraham, L. J., Garvie, C. W., and Hagman, J. (2003) Requirements for Selective Recruitment of Ets Proteins and Activation of Mb-1/Ig-Alpha Gene Transcription by Pax-5 (BSAP). Nucleic Acids Res. 31, 5483-5489.
37. Maitra, S., and Atchison, M. (2000) BSAP can Repress Enhancer Activity by Targeting PU.1 Function. Mol Cell Biol. 20, 1911-1922.
38. Linderson, Y., Eberhard, D., Malin, S., Johansson, A., Busslinger, M., and Pettersson, S. (2004) Corecruitment of the Grg4 Repressor by PU.1 is Critical for Pax5-Mediated Repression of B-Cell-Specific Genes. EMBO Rep. 5, 291-296.
39. Linderson, Y., French, N. S., Neurath, M. F., and Pettersson, S. (2001) Context-Dependent Pax-5 Repression of a PU.1/NF-kappaB Regulated Reporter Gene in B Lineage Cells. Gene. 262, 107-114.
40. Kishi, H., Jin, Z. X., Wei, X. C., Nagata, T., Matsuda, T., Saito, S., and Muraguchi, A. (2002) Cooperative Binding of c-Myb and Pax-5 Activates the RAG-2 Promoter in Immature B Cells. Blood. 99, 576-583.
41. Barlev, N. A., Emelyanov, A. V., Castagnino, P., Zegerman, P., Bannister, A. J., Sepulveda, M. A., Robert, F., Tora, L., Kouzarides, T., Birshtein, B. K., and Berger, S. L. (2003) A Novel Human Ada2 Homologue Functions with Gcn5 Or Brg1 to Coactivate Transcription. Mol Cell Biol. 23, 6944-6957.
42. Vidal, L. J., Perry, J. K., Vouyovitch, C. M., Pandey, V., Brunet-Dunand, S. E., Mertani, H. C., Liu, D. X., and Lobie, P. E. (2010) PAX5alpha Enhances the Epithelial Behavior of Human Mammary Carcinoma Cells. Mol Cancer Res. 8, 444-456.
43. Asano, M., and Gruss, P. (1992) Pax-5 is Expressed at the Midbrain-Hindbrain Boundary during Mouse Development. Mech Dev. 39, 29-39.
44. Urbanek, P., Wang, Z. Q., Fetka, I., Wagner, E. F., and Busslinger, M. (1994) Complete Block of Early B Cell Differentiation and Altered Patterning of the Posterior Midbrain in Mice Lacking Pax5/BSAP. Cell. 79, 901-912.
45. Pfeffer, P. L., Bouchard, M., and Busslinger, M. (2000) Pax2 and Homeodomain Proteins Cooperatively Regulate a 435 Bp Enhancer of the Mouse Pax5 Gene at the Midbrain-Hindbrain Boundary. Development. 127, 1017-1028.
46. Fuxa, M., and Busslinger, M. (2007) Reporter Gene Insertions Reveal a Strictly B Lymphoid-Specific Expression Pattern of Pax5 in Support of its B Cell Identity Function. J Immunol. 178, 8222-8228.
47. Revilla-I-Domingo, R., Bilic, I., Vilagos, B., Tagoh, H., Ebert, A., Tamir, I. M., Smeenk, L., Trupke, J., Sommer, A., Jaritz, M., and Busslinger, M. (2012) The B-Cell Identity Factor Pax5 Regulates Distinct Transcriptional Programmes in Early and Late B Lymphopoiesis. EMBO J. 31, 3130-3146.
48. Cobaleda, C., Schebesta, A., Delogu, A., and Busslinger, M. (2007) Pax5: The Guardian of B Cell Identity and Function. Nat Immunol. 8, 463-470.
49. Schebesta, M., Heavey, B., and Busslinger, M. (2002) Transcriptional Control of B-Cell Development. Curr Opin Immunol. 14, 216-223.
50. Nutt, S. L., Urbanek, P., Rolink, A., and Busslinger, M. (1997) Essential Functions of Pax5 (BSAP) in Pro-B Cell Development: Difference between Fetal and Adult B Lymphopoiesis and Reduced V-to-DJ Recombination at the IgH Locus. Genes Dev. 11, 476-491.
51. Barberis, A., Widenhorn, K., Vitelli, L., and Busslinger, M. (1990) A Novel B-Cell Lineage-Specific Transcription Factor Present at Early but Not Late Stages of Differentiation. Genes Dev. 4, 849-859.
52. Medvedovic, J., Ebert, A., Tagoh, H., and Busslinger, M. (2011) Pax5: A Master Regulator of B Cell Development and Leukemogenesis. Adv Immunol. 111, 179-206.
53. Bain, G., Maandag, E. C., Izon, D. J., Amsen, D., Kruisbeek, A. M., Weintraub, B. C., Krop, I., Schlissel, M. S., Feeney, A. J., and van Roon, M. (1994) E2A Proteins are Required for Proper B Cell Development and Initiation of Immunoglobulin Gene Rearrangements. Cell. 79, 885-892.
54. Lin, H., and Grosschedl, R. (1995) Failure of B-Cell Differentiation in Mice Lacking the Transcription Factor EBF. Nature. 376, 263-267.
55. Northrup, D. L., and Allman, D. (2008) Transcriptional Regulation of Early B Cell Development. Immunol Res. 42, 106-117.
56. Balasenthil, S., Gururaj, A. E., Talukder, A. H., Bagheri-Yarmand, R., Arrington, T., Haas, B. J., Braisted, J. C., Kim, I., Lee, N. H., and Kumar, R. (2007) Identification of Pax5 as a Target of MTA1 in B-Cell Lymphomas. Cancer Res. 67, 7132-7138.
57. Hirokawa, S., Sato, H., Kato, I., and Kudo, A. (2003) EBF-Regulating Pax5 Transcription is Enhanced by STAT5 in the Early Stage of B Cells. Eur J Immunol. 33, 1824-1829.
58. Vouyovitch, C. M., Vidal, L., Borges, S., Raccurt, M., Arnould, C., Chiesa, J., Lobie, P. E., Lachuer, J., and Mertani, H. C. (2008) Proteomic Analysis of autocrine/paracrine Effects of Human Growth Hormone in Human Mammary Carcinoma Cells. Adv Exp Med Biol. 617, 493-500.
59. McManus, S., Ebert, A., Salvagiotto, G., Medvedovic, J., Sun, Q., Tamir, I., Jaritz, M., Tagoh, H., and Busslinger, M. (2011) The Transcription Factor Pax5 Regulates its Target Genes by Recruiting Chromatin-Modifying Proteins in Committed B Cells. EMBO J. 30, 2388-2404.
60. Schebesta, A., McManus, S., Salvagiotto, G., Delogu, A., Busslinger, G. A., and Busslinger, M. (2007) Transcription Factor Pax5 Activates the Chromatin of Key Genes Involved in B Cell Signaling, Adhesion, Migration, and Immune Function. Immunity. 27, 49-63.
61. Pridans, C., Holmes, M. L., Polli, M., Wettenhall, J. M., Dakic, A., Corcoran, L. M., Smyth, G. K., and Nutt, S. L. (2008) Identification of Pax5 Target Genes in Early B Cell Differentiation. J Immunol. 180, 1719-1728.
62. Carotta, S., Holmes, M. L., Pridans, C., and Nutt, S. L. (2006) Pax5 Maintains Cellular Identity by Repressing Gene Expression Throughout B Cell Differentiation. Cell Cycle. 5, 2452-2456.
63. Johnson, K., and Calame, K. (2003) Transcription Factors Controlling the Beginning and End of B-Cell Differentiation. Curr Opin Genet Dev. 13, 522-528.
64. Nutt, S. L., and Kee, B. L. (2007) The Transcriptional Regulation of B Cell Lineage Commitment. Immunity. 26, 715-725.
65. Kozmik, Z., Wang, S., Dorfler, P., Adams, B., and Busslinger, M. (1992) The Promoter of the CD19 Gene is a Target for the B-Cell-Specific Transcription Factor BSAP. Mol Cell Biol. 12, 2662-2672.
66. Nutt, S. L., Morrison, A. M., Dorfler, P., Rolink, A., and Busslinger, M. (1998) Identification of BSAP (Pax-5) Target Genes in Early B-Cell Development by Loss- and Gain-of-Function Experiments. EMBO J. 17, 2319-2333.
67. Nutt, S. L., Heavey, B., Rolink, A. G., and Busslinger, M. (1999) Commitment to the B-Lymphoid Lineage Depends on the Transcription Factor Pax5. Nature. 401, 556-562.
68. Delogu, A., Schebesta, A., Sun, Q., Aschenbrenner, K., Perlot, T., and Busslinger, M. (2006) Gene Repression by Pax5 in B Cells is Essential for Blood Cell Homeostasis and is Reversed in Plasma Cells. Immunity. 24, 269-281.
69. Roessler, S., Gyory, I., Imhof, S., Spivakov, M., Williams, R. R., Busslinger, M., Fisher, A. G., and Grosschedl, R. (2007) Distinct Promoters Mediate the Regulation of Ebf1 Gene Expression by Interleukin-7 and Pax5. Mol Cell Biol. 27, 579-594.
70. Kee, B. L., and Murre, C. (1998) Induction of Early B Cell Factor (EBF) and Multiple B Lineage Genes by the Basic Helix-Loop-Helix Transcription Factor E12. J Exp Med. 188, 699-713.
71. Reimold, A. M., Ponath, P. D., Li, Y. S., Hardy, R. R., David, C. S., Strominger, J. L., and Glimcher, L. H. (1996) Transcription Factor B Cell Lineage-Specific Activator Protein Regulates the Gene for Human X-Box Binding Protein 1. J Exp Med. 183, 393-401.
72. Zwollo, P., and Desiderio, S. (1994) Specific Recognition of the Blk Promoter by the B-Lymphoid Transcription Factor B-Cell-Specific Activator Protein. J Biol Chem. 269, 15310-15317.
73. Schebesta, M., Pfeffer, P. L., and Busslinger, M. (2002) Control of Pre-BCR Signaling by Pax5-Dependent Activation of the BLNK Gene. Immunity. 17, 473-485.
74. Okabe, T., Bauer, S. R., and Kudo, A. (1992) Pre-B Lymphocyte-Specific Transcriptional Control of the Mouse VpreB Gene. Eur J Immunol. 22, 31-36.
75. Bougel, S., Renaud, S., Braunschweig, R., Loukinov, D., Morse, H. C.,3rd, Bosman, F. T., Lobanenkov, V., and Benhattar, J. (2010) PAX5 Activates the Transcription of the Human Telomerase Reverse Transcriptase Gene in B Cells. J Pathol. 220, 87-96.
76. Cobaleda, C., and Busslinger, M. (2008) Developmental Plasticity of Lymphocytes. Curr Opin Immunol. 20, 139-148.
77. Souabni, A., Cobaleda, C., Schebesta, M., and Busslinger, M. (2002) Pax5 Promotes B Lymphopoiesis and Blocks T Cell Development by Repressing Notch1. Immunity. 17, 781-793.
78. Mikkola, I., Heavey, B., Horcher, M., and Busslinger, M. (2002) Reversion of B Cell Commitment upon Loss of Pax5 Expression. Science. 297, 110-113.
79. Holmes, M. L., Carotta, S., Corcoran, L. M., and Nutt, S. L. (2006) Repression of Flt3 by Pax5 is Crucial for B-Cell Lineage Commitment. Genes Dev. 20, 933-938.
80. Tagoh, H., Ingram, R., Wilson, N., Salvagiotto, G., Warren, A. J., Clarke, D., Busslinger, M., and Bonifer, C. (2006) The Mechanism of Repression of the Myeloid-Specific c-Fms Gene by Pax5 during B Lineage Restriction. EMBO J. 25, 1070-1080.
81. Nera, K. P., Kohonen, P., Narvi, E., Peippo, A., Mustonen, L., Terho, P., Koskela, K., Buerstedde, J. M., and Lassila, O. (2006) Loss of Pax5 Promotes Plasma Cell Differentiation. Immunity. 24, 283-293.
82. Rinkenberger, J. L., Wallin, J. J., Johnson, K. W., and Koshland, M. E. (1996) An Interleukin-2 Signal Relieves BSAP (Pax5)-Mediated Repression of the Immunoglobulin J Chain Gene. Immunity. 5, 377-386.
83. Roldan, E., Fuxa, M., Chong, W., Martinez, D., Novatchkova, M., Busslinger, M., and Skok, J. A. (2005) Locus 'Decontraction' and Centromeric Recruitment Contribute to Allelic Exclusion of the Immunoglobulin Heavy-Chain Gene. Nat Immunol. 6, 31-41.
84. Sayegh, C. E., Jhunjhunwala, S., Riblet, R., and Murre, C. (2005) Visualization of Looping Involving the Immunoglobulin Heavy-Chain Locus in Developing B Cells. Genes Dev. 19, 322-327.
85. Fuxa, M., Skok, J., Souabni, A., Salvagiotto, G., Roldan, E., and Busslinger, M. (2004) Pax5 Induces V-to-DJ Rearrangements and Locus Contraction of the Immunoglobulin Heavy-Chain Gene. Genes Dev. 18, 411-422.
86. Horcher, M., Souabni, A., and Busslinger, M. (2001) Pax5/BSAP Maintains the Identity of B Cells in Late B Lymphopoiesis. Immunity. 14, 779-790.
87. Cobaleda, C., Jochum, W., and Busslinger, M. (2007) Conversion of Mature B Cells into T Cells by Dedifferentiation to Uncommitted Progenitors. Nature. 449, 473-477.
88. Hsu, L. Y., Liang, H. E., Johnson, K., Kang, C., and Schlissel, M. S. (2004) Pax5 Activates Immunoglobulin Heavy Chain V to DJ Rearrangement in Transgenic Thymocytes. J Exp Med. 199, 825-830.
89. Urbanek, P., Fetka, I., Meisler, M. H., and Busslinger, M. (1997) Cooperation of Pax2 and Pax5 in Midbrain and Cerebellum Development. Proc Natl Acad Sci U S A. 94, 5703-5708.
90. Funahashi, J., Okafuji, T., Ohuchi, H., Noji, S., Tanaka, H., and Nakamura, H. (1999) Role of Pax-5 in the Regulation of a Mid-Hindbrain Organizer's Activity. Dev Growth Differ. 41, 59-72.
91. Iida, S., Rao, P. H., Nallasivam, P., Hibshoosh, H., Butler, M., Louie, D. C., Dyomin, V., Ohno, H., Chaganti, R. S., and Dalla-Favera, R. (1996) The t(9;14)(p13;q32) Chromosomal Translocation Associated with Lymphoplasmacytoid Lymphoma Involves the PAX-5 Gene. Blood. 88, 4110-4117.
92. Morrison, A. M., Jager, U., Chott, A., Schebesta, M., Haas, O. A., and Busslinger, M. (1998) Deregulated PAX-5 Transcription from a Translocated IgH Promoter in Marginal Zone Lymphoma. Blood. 92, 3865-3878.
93. Cook, J. R., Aguilera, N. I., Reshmi-Skarja, S., Huang, X., Yu, Z., Gollin, S. M., Abbondanzo, S. L., and Swerdlow, S. H. (2004) Lack of PAX5 Rearrangements in Lymphoplasmacytic Lymphomas: Reassessing the Reported Association with t(9;14). Hum Pathol. 35, 447-454.
94. Poppe, B., De Paepe, P., Michaux, L., Dastugue, N., Bastard, C., Herens, C., Moreau, E., Cavazzini, F., Yigit, N., Van Limbergen, H., De Paepe, A., Praet, M., De Wolf-Peeters, C., Wlodarska, I., and Speleman, F. (2005) PAX5/IGH Rearrangement is a Recurrent Finding in a Subset of Aggressive B-NHL with Complex Chromosomal Rearrangements. Genes Chromosomes Cancer. 44, 218-223.
95. Mullighan, C. G., Goorha, S., Radtke, I., Miller, C. B., Coustan-Smith, E., Dalton, J. D., Girtman, K., Mathew, S., Ma, J., Pounds, S. B., Su, X., Pui, C. H., Relling, M. V., Evans, W. E., Shurtleff, S. A., and Downing, J. R. (2007) Genome-Wide Analysis of Genetic Alterations in Acute Lymphoblastic Leukaemia. Nature. 446, 758-764.
96. Gaidano, G., Pasqualucci, L., Capello, D., Berra, E., Deambrogi, C., Rossi, D., Maria Larocca, L., Gloghini, A., Carbone, A., and Dalla-Favera, R. (2003) Aberrant Somatic Hypermutation in Multiple Subtypes of AIDS-Associated Non-Hodgkin Lymphoma. Blood. 102, 1833-1841.
97. Krenacs, L., Himmelmann, A. W., Quintanilla-Martinez, L., Fest, T., Riva, A., Wellmann, A., Bagdi, E., Kehrl, J. H., Jaffe, E. S., and Raffeld, M. (1998) Transcription Factor B-Cell-Specific Activator Protein (BSAP) is Differentially Expressed in B Cells and in Subsets of B-Cell Lymphomas. Blood. 92, 1308-1316.
98. Reimer, K., Urbanek, P., Busslinger, M., and Ehret, G. (1996) Normal Brainstem Auditory Evoked Potentials in Pax5-Deficient Mice Despite Morphologic Alterations in the Auditory Midbrain Region. Audiology. 35, 55-61.
99. Rolink, A. G., Nutt, S. L., Melchers, F., and Busslinger, M. (1999) Long-Term in Vivo Reconstitution of T-Cell Development by Pax5-Deficient B-Cell Progenitors. Nature. 401, 603-606.
100. Schaniel, C., Bruno, L., Melchers, F., and Rolink, A. G. (2002) Multiple Hematopoietic Cell Lineages Develop in Vivo from Transplanted Pax5-Deficient Pre-B I-Cell Clones. Blood. 99, 472-478.
|Science Writers||Anne Murray|
|Illustrators||Diantha La Vine, Katherine Timer|
|Authors||Carrie Arnold and Elaine Pirie|
|List |< first << previous [record 19 of 511] next >> last >||