Incidental Mutation 'R0140:Abca2'
| ID |
22232 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Abca2
|
| Ensembl Gene |
ENSMUSG00000026944 |
| Gene Name |
ATP-binding cassette, sub-family A member 2 |
| Synonyms |
Abc2, D2H0S1474E |
| MMRRC Submission |
038425-MU
|
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
R0140 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
(trace)
|
| Chromosome |
2 |
| Chromosomal Location |
25318715-25338552 bp(+) (GRCm39) |
| Type of Mutation |
critical splice donor site (2 bp from exon) |
| DNA Base Change (assembly) |
T to G
at 25328097 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000099983
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000102919]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
probably null
Transcript: ENSMUST00000102919
|
| SMART Domains |
Protein: ENSMUSP00000099983
Gene: ENSMUSG00000026944
| Domain | Start | End | E-Value | Type |
|---|
|
transmembrane domain
|
21 |
40 |
N/A |
INTRINSIC |
|
low complexity region
|
119 |
130 |
N/A |
INTRINSIC |
|
low complexity region
|
220 |
237 |
N/A |
INTRINSIC |
|
coiled coil region
|
271 |
296 |
N/A |
INTRINSIC |
|
low complexity region
|
309 |
346 |
N/A |
INTRINSIC |
|
Pfam:ABC2_membrane_3
|
493 |
911 |
9.7e-18 |
PFAM |
|
AAA
|
1015 |
1197 |
9.22e-7 |
SMART |
|
low complexity region
|
1364 |
1376 |
N/A |
INTRINSIC |
|
low complexity region
|
1589 |
1607 |
N/A |
INTRINSIC |
|
Pfam:ABC2_membrane_3
|
1696 |
2008 |
2.3e-44 |
PFAM |
|
AAA
|
2079 |
2264 |
1.12e-5 |
SMART |
|
low complexity region
|
2375 |
2394 |
N/A |
INTRINSIC |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000143075
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000150550
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000199405
|
| Meta Mutation Damage Score |
0.9495 |
| Coding Region Coverage |
- 1x: 99.1%
- 3x: 98.4%
- 10x: 96.6%
- 20x: 93.4%
|
| Validation Efficiency |
98% (79/81) |
| MGI Phenotype |
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 |
All alleles(4) : Targeted(4)
|
| Other mutations in this stock |
Total: 72 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 2010315B03Rik |
T |
C |
9: 124,057,789 (GRCm39) |
|
probably benign |
Het |
| 9330161L09Rik |
T |
C |
12: 103,373,587 (GRCm39) |
|
probably benign |
Het |
| Adgrf3 |
T |
C |
5: 30,401,379 (GRCm39) |
K13R |
probably benign |
Het |
| Arhgap15 |
C |
A |
2: 44,212,779 (GRCm39) |
F416L |
probably damaging |
Het |
| Arhgef26 |
C |
G |
3: 62,355,666 (GRCm39) |
T746R |
probably benign |
Het |
| Aspm |
C |
T |
1: 139,408,379 (GRCm39) |
T2422I |
probably benign |
Het |
| Atp4a |
C |
G |
7: 30,419,526 (GRCm39) |
R659G |
probably benign |
Het |
| AY358078 |
T |
A |
14: 52,063,399 (GRCm39) |
D348E |
probably benign |
Het |
| Blnk |
A |
T |
19: 40,928,668 (GRCm39) |
S285T |
probably damaging |
Het |
| Calr3 |
C |
T |
8: 73,188,732 (GRCm39) |
|
probably benign |
Het |
| Camsap2 |
A |
T |
1: 136,208,120 (GRCm39) |
V1124D |
probably benign |
Het |
| Ccdc40 |
G |
A |
11: 119,155,125 (GRCm39) |
G1122S |
probably benign |
Het |
| Ccdc69 |
C |
A |
11: 54,941,325 (GRCm39) |
C196F |
possibly damaging |
Het |
| Cdhr3 |
T |
G |
12: 33,130,412 (GRCm39) |
N141T |
probably benign |
Het |
| Cdk4 |
T |
C |
10: 126,900,214 (GRCm39) |
V37A |
probably damaging |
Het |
| Celsr2 |
C |
T |
3: 108,305,249 (GRCm39) |
R2110K |
probably benign |
Het |
| Clcn7 |
A |
G |
17: 25,372,728 (GRCm39) |
Y437C |
probably damaging |
Het |
| Col6a6 |
A |
G |
9: 105,579,474 (GRCm39) |
F1917S |
probably damaging |
Het |
| Cps1 |
T |
G |
1: 67,219,275 (GRCm39) |
S872A |
probably benign |
Het |
| Crebbp |
G |
T |
16: 3,935,363 (GRCm39) |
T842N |
probably damaging |
Het |
| Dennd2d |
G |
A |
3: 106,399,799 (GRCm39) |
V234I |
probably benign |
Het |
| Fam227b |
T |
C |
2: 125,966,523 (GRCm39) |
M130V |
possibly damaging |
Het |
| Fbxw24 |
G |
T |
9: 109,434,482 (GRCm39) |
L373I |
possibly damaging |
Het |
| Fubp3 |
T |
C |
2: 31,498,196 (GRCm39) |
Y359H |
probably damaging |
Het |
| Gm19684 |
T |
C |
17: 36,438,319 (GRCm39) |
|
probably benign |
Het |
| Hrnr |
C |
T |
3: 93,238,800 (GRCm39) |
Q3013* |
probably null |
Het |
| Il12rb1 |
T |
C |
8: 71,272,415 (GRCm39) |
|
probably benign |
Het |
| Lepr |
A |
T |
4: 101,625,264 (GRCm39) |
D473V |
probably damaging |
Het |
| Myof |
A |
T |
19: 37,940,004 (GRCm39) |
Y820* |
probably null |
Het |
| Nfil3 |
G |
A |
13: 53,121,681 (GRCm39) |
Q408* |
probably null |
Het |
| Nolc1 |
G |
A |
19: 46,069,817 (GRCm39) |
|
probably benign |
Het |
| Npbwr1 |
A |
C |
1: 5,986,840 (GRCm39) |
Y225D |
probably damaging |
Het |
| Nrip3 |
T |
C |
7: 109,361,022 (GRCm39) |
|
probably benign |
Het |
| Ntrk1 |
A |
C |
3: 87,685,875 (GRCm39) |
L749R |
probably damaging |
Het |
| Or10ag53 |
A |
G |
2: 87,082,969 (GRCm39) |
I229M |
probably damaging |
Het |
| Or2b11 |
A |
G |
11: 59,461,804 (GRCm39) |
L254P |
probably damaging |
Het |
| Or4c126 |
T |
A |
2: 89,824,463 (GRCm39) |
V242D |
probably damaging |
Het |
| Or52a24 |
A |
G |
7: 103,381,349 (GRCm39) |
D72G |
probably damaging |
Het |
| Or6c211 |
G |
T |
10: 129,505,557 (GRCm39) |
T277N |
probably damaging |
Het |
| Paox |
A |
T |
7: 139,713,971 (GRCm39) |
T244S |
probably damaging |
Het |
| Pcdhb9 |
T |
A |
18: 37,536,014 (GRCm39) |
D669E |
possibly damaging |
Het |
| Pggt1b |
A |
G |
18: 46,391,150 (GRCm39) |
|
probably null |
Het |
| Phkg1 |
T |
A |
5: 129,893,449 (GRCm39) |
I334F |
probably benign |
Het |
| Phtf1 |
A |
T |
3: 103,894,876 (GRCm39) |
R208W |
probably null |
Het |
| Pnliprp2 |
A |
T |
19: 58,754,795 (GRCm39) |
I280F |
probably benign |
Het |
| Pnma8a |
A |
G |
7: 16,694,147 (GRCm39) |
M1V |
probably null |
Het |
| Prcp |
A |
G |
7: 92,577,819 (GRCm39) |
T328A |
probably damaging |
Het |
| Pxdn |
A |
G |
12: 30,032,753 (GRCm39) |
E179G |
probably benign |
Het |
| Racgap1 |
A |
T |
15: 99,521,532 (GRCm39) |
N541K |
probably benign |
Het |
| Rnf103 |
T |
A |
6: 71,486,315 (GRCm39) |
F315L |
possibly damaging |
Het |
| Septin2 |
A |
G |
1: 93,429,361 (GRCm39) |
R237G |
probably damaging |
Het |
| Setd6 |
T |
A |
8: 96,442,737 (GRCm39) |
L58Q |
probably damaging |
Het |
| Sipa1l1 |
G |
A |
12: 82,442,974 (GRCm39) |
V755I |
probably damaging |
Het |
| Slc16a12 |
G |
T |
19: 34,650,104 (GRCm39) |
|
probably benign |
Het |
| Slk |
G |
A |
19: 47,610,774 (GRCm39) |
D815N |
probably damaging |
Het |
| Stx1a |
T |
C |
5: 135,074,439 (GRCm39) |
|
probably benign |
Het |
| Tbc1d15 |
T |
A |
10: 115,056,124 (GRCm39) |
I283F |
probably damaging |
Het |
| Tenm4 |
T |
C |
7: 96,545,259 (GRCm39) |
I2425T |
possibly damaging |
Het |
| Tle1 |
G |
A |
4: 72,038,422 (GRCm39) |
H702Y |
probably damaging |
Het |
| Tmc6 |
A |
G |
11: 117,657,077 (GRCm39) |
|
probably benign |
Het |
| Tmem268 |
G |
A |
4: 63,496,096 (GRCm39) |
R179H |
possibly damaging |
Het |
| Tmem9 |
A |
G |
1: 135,961,900 (GRCm39) |
K165R |
probably damaging |
Het |
| Trpm6 |
A |
G |
19: 18,796,558 (GRCm39) |
|
probably null |
Het |
| Tufm |
C |
T |
7: 126,089,003 (GRCm39) |
P88S |
probably damaging |
Het |
| Ubqln1 |
A |
G |
13: 58,341,103 (GRCm39) |
I216T |
probably damaging |
Het |
| Urad |
T |
G |
5: 147,259,141 (GRCm39) |
M1L |
probably benign |
Het |
| Utp6 |
A |
G |
11: 79,847,551 (GRCm39) |
|
probably benign |
Het |
| Vav2 |
C |
T |
2: 27,163,688 (GRCm39) |
|
probably benign |
Het |
| Vmn2r55 |
G |
T |
7: 12,402,104 (GRCm39) |
Q395K |
possibly damaging |
Het |
| Wwox |
T |
G |
8: 115,433,027 (GRCm39) |
V231G |
probably damaging |
Het |
| Zfp646 |
T |
A |
7: 127,482,678 (GRCm39) |
N1618K |
probably benign |
Het |
| Zzef1 |
G |
A |
11: 72,790,377 (GRCm39) |
M2110I |
possibly damaging |
Het |
|
| Other mutations in Abca2 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00093:Abca2
|
APN |
2 |
25,335,975 (GRCm39) |
splice site |
probably null |
|
|
IGL01102:Abca2
|
APN |
2 |
25,323,968 (GRCm39) |
splice site |
probably benign |
|
|
IGL01322:Abca2
|
APN |
2 |
25,336,794 (GRCm39) |
splice site |
probably null |
|
|
IGL01402:Abca2
|
APN |
2 |
25,332,015 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01419:Abca2
|
APN |
2 |
25,327,526 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01490:Abca2
|
APN |
2 |
25,336,023 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01633:Abca2
|
APN |
2 |
25,334,406 (GRCm39) |
missense |
possibly damaging |
0.66 |
|
IGL01661:Abca2
|
APN |
2 |
25,333,007 (GRCm39) |
missense |
probably benign |
0.01 |
|
IGL01804:Abca2
|
APN |
2 |
25,336,637 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01933:Abca2
|
APN |
2 |
25,334,123 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01941:Abca2
|
APN |
2 |
25,333,107 (GRCm39) |
missense |
probably benign |
0.02 |
|
IGL02158:Abca2
|
APN |
2 |
25,337,891 (GRCm39) |
utr 3 prime |
probably benign |
|
|
IGL02173:Abca2
|
APN |
2 |
25,331,909 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL02419:Abca2
|
APN |
2 |
25,336,849 (GRCm39) |
missense |
probably benign |
|
|
IGL02532:Abca2
|
APN |
2 |
25,325,148 (GRCm39) |
missense |
probably benign |
0.03 |
|
IGL02572:Abca2
|
APN |
2 |
25,323,329 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
Abseiling
|
UTSW |
2 |
25,337,015 (GRCm39) |
missense |
possibly damaging |
0.65 |
|
R0126:Abca2
|
UTSW |
2 |
25,333,742 (GRCm39) |
missense |
possibly damaging |
0.88 |
|
R0372:Abca2
|
UTSW |
2 |
25,327,365 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0437:Abca2
|
UTSW |
2 |
25,332,857 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R0505:Abca2
|
UTSW |
2 |
25,324,906 (GRCm39) |
missense |
probably benign |
0.22 |
|
R0570:Abca2
|
UTSW |
2 |
25,337,417 (GRCm39) |
splice site |
probably null |
|
|
R1037:Abca2
|
UTSW |
2 |
25,328,240 (GRCm39) |
splice site |
probably benign |
|
|
R1283:Abca2
|
UTSW |
2 |
25,336,701 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1448:Abca2
|
UTSW |
2 |
25,330,542 (GRCm39) |
missense |
possibly damaging |
0.73 |
|
R1464:Abca2
|
UTSW |
2 |
25,337,846 (GRCm39) |
splice site |
probably benign |
|
|
R1468:Abca2
|
UTSW |
2 |
25,331,308 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1468:Abca2
|
UTSW |
2 |
25,331,308 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1480:Abca2
|
UTSW |
2 |
25,323,409 (GRCm39) |
missense |
possibly damaging |
0.60 |
|
R1545:Abca2
|
UTSW |
2 |
25,332,370 (GRCm39) |
missense |
probably benign |
0.17 |
|
R1562:Abca2
|
UTSW |
2 |
25,336,331 (GRCm39) |
missense |
probably benign |
0.43 |
|
R1569:Abca2
|
UTSW |
2 |
25,329,197 (GRCm39) |
missense |
probably benign |
0.45 |
|
R1586:Abca2
|
UTSW |
2 |
25,337,228 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R1635:Abca2
|
UTSW |
2 |
25,334,868 (GRCm39) |
missense |
probably benign |
0.03 |
|
R1699:Abca2
|
UTSW |
2 |
25,337,363 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
R1754:Abca2
|
UTSW |
2 |
25,324,345 (GRCm39) |
missense |
probably benign |
0.01 |
|
R1760:Abca2
|
UTSW |
2 |
25,333,055 (GRCm39) |
missense |
probably benign |
0.00 |
|
R2040:Abca2
|
UTSW |
2 |
25,333,817 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2067:Abca2
|
UTSW |
2 |
25,327,517 (GRCm39) |
missense |
possibly damaging |
0.88 |
|
R2111:Abca2
|
UTSW |
2 |
25,327,517 (GRCm39) |
missense |
possibly damaging |
0.88 |
|
R2248:Abca2
|
UTSW |
2 |
25,323,476 (GRCm39) |
splice site |
probably benign |
|
|
R2323:Abca2
|
UTSW |
2 |
25,335,187 (GRCm39) |
missense |
probably benign |
0.00 |
|
R2418:Abca2
|
UTSW |
2 |
25,328,001 (GRCm39) |
missense |
probably benign |
0.22 |
|
R2419:Abca2
|
UTSW |
2 |
25,328,001 (GRCm39) |
missense |
probably benign |
0.22 |
|
R3816:Abca2
|
UTSW |
2 |
25,336,083 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4180:Abca2
|
UTSW |
2 |
25,331,590 (GRCm39) |
missense |
possibly damaging |
0.58 |
|
R4431:Abca2
|
UTSW |
2 |
25,332,864 (GRCm39) |
missense |
probably benign |
|
|
R4468:Abca2
|
UTSW |
2 |
25,334,914 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4704:Abca2
|
UTSW |
2 |
25,333,424 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R4839:Abca2
|
UTSW |
2 |
25,330,921 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R4933:Abca2
|
UTSW |
2 |
25,334,839 (GRCm39) |
missense |
probably benign |
0.25 |
|
R4970:Abca2
|
UTSW |
2 |
25,328,383 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4971:Abca2
|
UTSW |
2 |
25,332,006 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R5112:Abca2
|
UTSW |
2 |
25,328,383 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5327:Abca2
|
UTSW |
2 |
25,335,686 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5378:Abca2
|
UTSW |
2 |
25,336,080 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5648:Abca2
|
UTSW |
2 |
25,326,510 (GRCm39) |
critical splice donor site |
probably null |
|
|
R5725:Abca2
|
UTSW |
2 |
25,329,412 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R5825:Abca2
|
UTSW |
2 |
25,326,748 (GRCm39) |
missense |
probably benign |
0.36 |
|
R5837:Abca2
|
UTSW |
2 |
25,323,371 (GRCm39) |
missense |
probably benign |
0.34 |
|
R5840:Abca2
|
UTSW |
2 |
25,323,371 (GRCm39) |
missense |
probably benign |
0.34 |
|
R5851:Abca2
|
UTSW |
2 |
25,332,322 (GRCm39) |
missense |
possibly damaging |
0.58 |
|
R6262:Abca2
|
UTSW |
2 |
25,334,922 (GRCm39) |
missense |
possibly damaging |
0.56 |
|
R6344:Abca2
|
UTSW |
2 |
25,327,706 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6547:Abca2
|
UTSW |
2 |
25,323,350 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
R6640:Abca2
|
UTSW |
2 |
25,337,015 (GRCm39) |
missense |
possibly damaging |
0.65 |
|
R6980:Abca2
|
UTSW |
2 |
25,330,878 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R6981:Abca2
|
UTSW |
2 |
25,334,151 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7070:Abca2
|
UTSW |
2 |
25,333,007 (GRCm39) |
missense |
probably benign |
0.06 |
|
R7080:Abca2
|
UTSW |
2 |
25,336,116 (GRCm39) |
missense |
probably benign |
0.37 |
|
R7187:Abca2
|
UTSW |
2 |
25,327,733 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7195:Abca2
|
UTSW |
2 |
25,332,088 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7297:Abca2
|
UTSW |
2 |
25,332,088 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7487:Abca2
|
UTSW |
2 |
25,327,915 (GRCm39) |
missense |
probably benign |
0.02 |
|
R7561:Abca2
|
UTSW |
2 |
25,336,707 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R7766:Abca2
|
UTSW |
2 |
25,331,540 (GRCm39) |
missense |
probably benign |
0.04 |
|
R8084:Abca2
|
UTSW |
2 |
25,323,979 (GRCm39) |
missense |
probably benign |
0.32 |
|
R8150:Abca2
|
UTSW |
2 |
25,337,393 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8684:Abca2
|
UTSW |
2 |
25,336,508 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R8753:Abca2
|
UTSW |
2 |
25,332,706 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8970:Abca2
|
UTSW |
2 |
25,335,728 (GRCm39) |
missense |
probably benign |
0.12 |
|
R9057:Abca2
|
UTSW |
2 |
25,331,584 (GRCm39) |
missense |
probably benign |
0.05 |
|
R9378:Abca2
|
UTSW |
2 |
25,329,094 (GRCm39) |
missense |
probably benign |
0.02 |
|
R9502:Abca2
|
UTSW |
2 |
25,326,895 (GRCm39) |
nonsense |
probably null |
|
|
R9688:Abca2
|
UTSW |
2 |
25,324,459 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R9770:Abca2
|
UTSW |
2 |
25,328,979 (GRCm39) |
critical splice donor site |
probably null |
|
|
RF063:Abca2
|
UTSW |
2 |
25,337,409 (GRCm39) |
missense |
probably damaging |
1.00 |
|
RF064:Abca2
|
UTSW |
2 |
25,337,409 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Z1176:Abca2
|
UTSW |
2 |
25,334,122 (GRCm39) |
missense |
probably benign |
0.39 |
|
| Predicted Primers |
PCR Primer
(F):5'- ACCATCCAGCATATTGTGGCAGAG -3'
(R):5'- GGCCAACTTAGCCTTAGAGTACAGC -3'
Sequencing Primer
(F):5'- TGCCCCACAGGTGATGAAG -3'
(R):5'- TTAGCCTTAGAGTACAGCACAGAC -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
involves: 129/Sv
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).
|
| References |
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. 6. Sakai, H., Tanaka, Y., Tanaka, M., Ban, N., Yamada, K., Matsumura, Y., Watanabe, D., Sasaki, M., Kita, T., and Inagaki, N. (2007) ABCA2 Deficiency Results in Abnormal Sphingolipid Metabolism in Mouse Brain. J Biol Chem. 282, 19692-19699. |
| Posted On |
2013-04-16 |
| Science Writer |
Anne Murray |
Incidental Mutation