|Institutional Source||Beutler Lab|
|Gene Name||ATP-binding cassette, sub-family A (ABC1), member 2|
|Is this an essential gene?||Non essential (E-score: 0.000)|
|Stock #||R0372 (G1)|
|Chromosomal Location||25428703-25448540 bp(+) (GRCm38)|
|Type of Mutation||missense|
|DNA Base Change (assembly)||A to G at 25437353 bp|
|Amino Acid Change||Tyrosine to Cysteine at position 641 (Y641C)|
|Ref Sequence||ENSEMBL: ENSMUSP00000099983 (fasta)|
|Gene Model||predicted gene model for transcript(s): [ENSMUST00000102919]|
|Predicted Effect||probably damaging
AA Change: Y641C
PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
AA Change: Y641C
|Predicted Effect||noncoding transcript
|Meta Mutation Damage Score||0.512|
|Coding Region Coverage||
|Validation Efficiency||97% (70/72)|
|MGI Phenotype||Strain: 3697467; 3719855
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This protein is highly expressed in brain tissue and may play a role in macrophage lipid metabolism and neural development. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
PHENOTYPE: Null mice show tremors, hyperactivity, abnormal coordination, and alterations in CNS myelin sheath ultrastructure, [provided by MGI curators]
|Allele List at MGI|
|Other mutations in this stock||
|Other mutations in Abca2||
(F):5'- TGCTTCAGTTTGCTCCCACAGG -3'
(R):5'- CCATGCACAATGGCATCATGTGTTC -3'
(F):5'- AGTGCTCACCTCACTGTGTC -3'
(R):5'- GAACATCTGCACGTAGTTGCC -3'
|Protein Function and Prediction|
Abca2 encodes ABCA2, a member of the A subfamily of ATP-binding cassette (ABC) transporters that function to translocate molecules across cellular membranes. ABCA2 functions in trafficking low-density lipoprotein (LDL)-derived free cholesterol (1). The ABCA2 protein has two transmembrane domains and two ABCs, the ABC consensus sequence is comprised of Walker A and Walker B motifs separated by 90-120 amino acids (2). Reverse transcriptase-PCR ELISA detected ABCA2 in all human adult and fetal tissues examined (lung, kidney, heart, liver, ovary, skeletal muscle, brain, pancreas, testis, spleen and liver); highest expression was in the brain and spinal cord (3). Additional studies determined that ABCA2 is most abundant in the central nervous system, ovary, and macrophages (4). ABCA2 colocalizes with the lysosomal/endosomal marker LAMP1 (4). ABCA2 expression has been linked with gene cluster patterns consistent with Alzheimer’s disease.
Abca2tm1Kdt/tm1Kdt; MGI: 3697467
Homozygotes exhibit decreased body weight compared to controls as well as increased fear-related responses, increased startle reflex to sound, tremors, impaired ability to counterbalance, hyperactivity, and increased rearing and climbing behavior (5). Homozygotes also have abnormal myeline sheath morphology: average myelin sheath thickness in the spinal cord is increased and there is reduced periodicity and compaction of myelin (5).
Abca2tm1Nina/tm1Nina; MGI: 3719855
involves: 129X1/SvJ * C57BL/6
Homozygotes exhibit increased morbidity/mortality when moved onto wet sawdust, tremors, impaired balance, abnormal sphingomyelin in their brain after growth stage, and increased levels of ganglioside GM1, cerebrosides and silfatide levels (6). In addition, homozygotes have decreased body weight (6). Female homozygotes have reduced female fertility (6).
1. Davis, W.,Jr, Boyd, J. T., Ile, K. E., and Tew, K. D. (2004) Human ATP-Binding Cassette Transporter-2 (ABCA2) Positively Regulates Low-Density Lipoprotein Receptor Expression and Negatively Regulates Cholesterol Esterification in Chinese Hamster Ovary Cells. Biochim Biophys Acta. 1683, 89-100.
2. Holland, I. B., and Blight, M. A. (1999) ABC-ATPases, Adaptable Energy Generators Fuelling Transmembrane Movement of a Variety of Molecules in Organisms from Bacteria to Humans. J Mol Biol. 293, 381-399.
3. Kikuno, R., Nagase, T., Ishikawa, K., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., and Ohara, O. (1999) Prediction of the Coding Sequences of Unidentified Human Genes. XIV. the Complete Sequences of 100 New cDNA Clones from Brain which Code for Large Proteins in Vitro. DNA Res. 6, 197-205.
4. Vulevic, B., Chen, Z., Boyd, J. T., Davis, W.,Jr, Walsh, E. S., Belinsky, M. G., and Tew, K. D. (2001) Cloning and Characterization of Human Adenosine 5'-Triphosphate-Binding Cassette, Sub-Family A, Transporter 2 (ABCA2). Cancer Res. 61, 3339-3347.
5. Mack, J. T., Beljanski, V., Soulika, A. M., Townsend, D. M., Brown, C. B., Davis, W., and Tew, K. D. (2007) "Skittish" Abca2 Knockout Mice Display Tremor, Hyperactivity, and Abnormal Myelin Ultrastructure in the Central Nervous System. Mol Cell Biol. 27, 44-53.
|Science Writer||Anne Murray|