|Coordinate||34,248,636 bp (GRCm38)|
|Base Change||G ⇒ A (forward strand)|
|Gene Name||dedicator of cyto-kinesis 2|
|Synonym(s)||CED-5, MBC, Hch|
|Chromosomal Location||34,226,815-34,783,892 bp (-)|
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the CDM protein family. It is specifically expressed in hematopoietic cells and is predominantly expressed in peripheral blood leukocytes. The protein is involved in remodeling of the actin cytoskeleton required for lymphocyte migration in response to chemokine signaling. It activates members of the Rho family of GTPases, for example RAC1 and RAC2, by acting as a guanine nucleotide exchange factor (GEF) to exchange bound GDP for free GTP. [provided by RefSeq, Oct 2016]
PHENOTYPE: Homozygous mutants are defective in the migration of T and B lympohcytes in response to chemokines, and thus display immune defects such as lymphocytopenia, atrophy of lymphoid follicles and loss of marginal-zone B cells. [provided by MGI curators]
|Amino Acid Change||Glutamine changed to Stop codon|
|Institutional Source||Beutler Lab|
|Gene Model||not available|
AA Change: Q1439*
|Predicted Effect||probably null|
|Meta Mutation Damage Score||Not available|
|Is this an essential gene?||Non Essential (E-score: 0.000)|
|Phenotypic Category||Autosomal Recessive|
|Candidate Explorer Status||CE: no linkage results|
Linkage Analysis Data
|Alleles Listed at MGI|
|Mode of Inheritance||Autosomal Recessive|
|Local Stock||Live Mice, Sperm|
|Last Updated||2019-05-21 7:40 PM by Diantha La Vine|
|Record Created||2010-10-11 7:39 PM by Carrie N. Arnold|
|Other Mutations in This Stock||
Stock #: I2505 Run Code: SLD00273
Validation Efficiency: 113/115
The dew mutation was identified in a T-dependent Humoral Response Screen of N-ethyl-N-nitrosourea (ENU)-mutagenized G3 mice (Figure 1). The dew mice lack a T-dependent IgG response (Figure 2); the T-independent IgM response is normal. Fluorescence activated cell sorting (FACS) analysis determined that CD4+ and CD8+ T cells are depleted in the dew mice (Figure 3).
|Nature of Mutation|
Whole genome sequencing of a homozygous dew mouse using the SOLiD technique identified a C to T transition at base pair 34148636 on Chromosome 11 in the GenBank genomic region NC_000077 encoding Dock2. The mutation corresponds to residue 4367 of the mRNA sequence NM_033374 in exon 43 (of 52).
The mutated nucleotide is indicated in red lettering and results in substitution of glutamine (Q) 1439 for a premature stop codon.
|Illustration of Mutations in
Gene & Protein
The dew mutation results in a coding of a premature stop codon at amino acid 1439 within the catalytic DOCK homology region 2 (DHR-2), a domain essential for the interaction of Dock2 with GTPases [Figure 5; (1;2)].
For more information on Dock2, see the record for frazz.
|Primers||Primers cannot be located by automatic search.|
Dew(F): 5’- AGAAGACCCAGTAGACTTGTCACCC -3’
Dew(R): 5’- AATGCCAGAATTGCAAATGCCCAG -3’
1) 95°C 2:00
2) 95°C 0:30
3) 56°C 0:30
4) 72°C 1:00
5) repeat steps (2-4) 29X
6) 72°C 7:00
7) 4°C 8
Primers for sequencing
Dew_seq(F): 5'- AGTAGACTTGTCACCCTATCTGG -3'
The following sequence of 415 nucleotides is amplified (Chr. 11: 34248432-34248846, GRCm38.; NC_000077):
agaagaccca gtagacttgt caccctatct gggatgtcca tgtagtattc actccctggc tctggatcaa gctgccccca cctgtggttg gcagaggtgt gttctggttg ctgaagatgg ctgaggaggg gattatactc acagcaaact cgttctctgg gtctaccttg cccctgcgca caggcctgga gtagtggaac ttttgcacat aattagactt gtaaaagctg aaagacagaa aggagtagaa gtttctggaa gccatgctac ccatccactg aaaccttaaa catcaggtct ggcagggccc tggcagtggc atttcaaggt ctgagttggg gcttcataaa aagtgatttg cacagggttg cagggtgatt tagaagccac cctgggcatt tgcaattctg gcatt
Primer binding sites are underlined; sequencing primer binding sites are highlighted in gray; the mutated nucleotide is indicated in red (G>A on Chr. + strand; C>T on sense strand).
1. Brugnera, E., Haney, L., Grimsley, C., Lu, M., Walk, S. F., Tosello-Trampont, A. C., Macara, I. G., Madhani, H., Fink, G. R., and Ravichandran, K. S. (2002) Unconventional Rac-GEF Activity is Mediated through the Dock180-ELMO Complex. Nat Cell Biol. 4, 574-582.
|Science Writers||Anne Murray|
|Authors||Carrie Arnold, Elaine Pirie, Ming Zeng and Bruce Beutler|