Incidental Mutation 'P0017:Crb1'
ID |
7823 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Crb1
|
Ensembl Gene |
ENSMUSG00000063681 |
Gene Name |
crumbs family member 1, photoreceptor morphogenesis associated |
Synonyms |
A930008G09Rik, 7530426H14Rik |
MMRRC Submission |
038270-MU
|
Accession Numbers |
|
Essential gene? |
Possibly non essential
(E-score: 0.303)
|
Stock # |
P0017 (G1)
|
Quality Score |
|
Status
|
Validated
|
Chromosome |
1 |
Chromosomal Location |
139124794-139304838 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
T to C
at 139176678 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Glutamic Acid to Glycine
at position 435
(E435G)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000142702
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000059825]
[ENSMUST00000196402]
[ENSMUST00000198445]
[ENSMUST00000200340]
|
AlphaFold |
Q8VHS2 |
Predicted Effect |
possibly damaging
Transcript: ENSMUST00000059825
AA Change: E435G
PolyPhen 2
Score 0.638 (Sensitivity: 0.87; Specificity: 0.91)
|
SMART Domains |
Protein: ENSMUSP00000060769 Gene: ENSMUSG00000063681 AA Change: E435G
Domain | Start | End | E-Value | Type |
low complexity region
|
8 |
19 |
N/A |
INTRINSIC |
EGF
|
72 |
107 |
5.97e-4 |
SMART |
EGF
|
112 |
145 |
9.19e-5 |
SMART |
EGF_CA
|
147 |
183 |
2.89e-11 |
SMART |
EGF_CA
|
185 |
221 |
1.14e-9 |
SMART |
EGF_CA
|
223 |
259 |
2.26e-13 |
SMART |
EGF_CA
|
261 |
298 |
5.15e-8 |
SMART |
EGF
|
303 |
336 |
8.12e-6 |
SMART |
EGF
|
341 |
394 |
2.6e-4 |
SMART |
EGF_CA
|
396 |
438 |
2.54e-7 |
SMART |
EGF
|
443 |
480 |
1.47e-3 |
SMART |
LamG
|
505 |
650 |
1.75e-9 |
SMART |
EGF
|
674 |
707 |
6.5e-5 |
SMART |
LamG
|
734 |
859 |
1.05e-7 |
SMART |
EGF
|
889 |
922 |
1.19e-3 |
SMART |
LamG
|
971 |
1104 |
6.85e-12 |
SMART |
EGF
|
1141 |
1174 |
7.07e-6 |
SMART |
EGF_CA
|
1176 |
1211 |
3.01e-9 |
SMART |
EGF
|
1216 |
1249 |
3.57e-2 |
SMART |
EGF
|
1257 |
1294 |
6.92e0 |
SMART |
EGF_CA
|
1296 |
1332 |
4.19e-8 |
SMART |
transmembrane domain
|
1346 |
1368 |
N/A |
INTRINSIC |
|
Predicted Effect |
possibly damaging
Transcript: ENSMUST00000196402
AA Change: E435G
PolyPhen 2
Score 0.638 (Sensitivity: 0.87; Specificity: 0.91)
|
SMART Domains |
Protein: ENSMUSP00000142702 Gene: ENSMUSG00000063681 AA Change: E435G
Domain | Start | End | E-Value | Type |
low complexity region
|
8 |
19 |
N/A |
INTRINSIC |
EGF
|
72 |
107 |
5.97e-4 |
SMART |
EGF
|
112 |
145 |
9.19e-5 |
SMART |
EGF_CA
|
147 |
183 |
2.89e-11 |
SMART |
EGF_CA
|
185 |
221 |
1.14e-9 |
SMART |
EGF_CA
|
223 |
259 |
2.26e-13 |
SMART |
EGF_CA
|
261 |
298 |
5.15e-8 |
SMART |
EGF
|
303 |
336 |
8.12e-6 |
SMART |
EGF
|
341 |
394 |
2.6e-4 |
SMART |
EGF_CA
|
396 |
438 |
2.54e-7 |
SMART |
EGF
|
443 |
480 |
1.47e-3 |
SMART |
LamG
|
505 |
650 |
1.75e-9 |
SMART |
EGF
|
674 |
707 |
6.5e-5 |
SMART |
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000197035
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000198445
AA Change: E374G
PolyPhen 2
Score 0.421 (Sensitivity: 0.89; Specificity: 0.90)
|
SMART Domains |
Protein: ENSMUSP00000142552 Gene: ENSMUSG00000063681 AA Change: E374G
Domain | Start | End | E-Value | Type |
low complexity region
|
8 |
19 |
N/A |
INTRINSIC |
EGF
|
72 |
107 |
5.97e-4 |
SMART |
EGF
|
112 |
145 |
9.19e-5 |
SMART |
EGF_CA
|
147 |
183 |
2.89e-11 |
SMART |
EGF_CA
|
185 |
221 |
1.14e-9 |
SMART |
EGF_CA
|
223 |
259 |
2.26e-13 |
SMART |
EGF_CA
|
261 |
298 |
5.15e-8 |
SMART |
EGF
|
303 |
333 |
1.63e1 |
SMART |
EGF_CA
|
335 |
377 |
2.54e-7 |
SMART |
EGF
|
382 |
419 |
1.47e-3 |
SMART |
LamG
|
444 |
589 |
1.75e-9 |
SMART |
EGF
|
613 |
646 |
6.5e-5 |
SMART |
LamG
|
673 |
798 |
1.05e-7 |
SMART |
EGF
|
828 |
861 |
1.19e-3 |
SMART |
LamG
|
910 |
1043 |
6.85e-12 |
SMART |
EGF
|
1080 |
1113 |
7.07e-6 |
SMART |
EGF_CA
|
1115 |
1150 |
3.01e-9 |
SMART |
EGF
|
1155 |
1188 |
3.57e-2 |
SMART |
EGF
|
1196 |
1233 |
6.92e0 |
SMART |
EGF_CA
|
1235 |
1271 |
4.19e-8 |
SMART |
low complexity region
|
1282 |
1296 |
N/A |
INTRINSIC |
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000199291
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000200340
|
SMART Domains |
Protein: ENSMUSP00000142909 Gene: ENSMUSG00000063681
Domain | Start | End | E-Value | Type |
EGF_CA
|
12 |
49 |
5.15e-8 |
SMART |
EGF
|
54 |
88 |
1.47e1 |
SMART |
|
Meta Mutation Damage Score |
0.1795 |
Coding Region Coverage |
- 1x: 82.5%
- 3x: 74.9%
- 10x: 52.3%
- 20x: 31.8%
|
Validation Efficiency |
59% (51/87) |
MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein which is similar to the Drosophila crumbs protein and localizes to the inner segment of mammalian photoreceptors. In Drosophila crumbs localizes to the stalk of the fly photoreceptor and may be a component of the molecular scaffold that controls proper development of polarity in the eye. Mutations in this gene are associated with a severe form of retinitis pigmentosa, RP12, and with Leber congenital amaurosis. Alternate splicing results in multiple transcript variants, some protein coding and some non-protein coding.[provided by RefSeq, Apr 2012] PHENOTYPE: Homozygotes for a null allele show focal retinal lesions, loss of adherens junctions between photoreceptors and Muller glia cells, and light-accelerated retinal degeneration. Homozygotes for a spontaneous allele show background-sensitive retinal spotting, photoreceptor dysplasia and degeneration. [provided by MGI curators]
|
Allele List at MGI |
All alleles(5) : Targeted(4) Spontaneous(1)
|
Other mutations in this stock |
Total: 6 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Ano4 |
A |
T |
10: 88,817,052 (GRCm39) |
L591* |
probably null |
Het |
Arhgap30 |
C |
T |
1: 171,236,272 (GRCm39) |
P882L |
probably benign |
Het |
C030017K20Rik |
G |
T |
4: 155,547,574 (GRCm39) |
|
probably null |
Het |
Fam193a |
G |
T |
5: 34,597,807 (GRCm39) |
D535Y |
probably damaging |
Het |
Hmcn1 |
T |
A |
1: 150,596,440 (GRCm39) |
T1799S |
possibly damaging |
Het |
Il20ra |
A |
G |
10: 19,635,154 (GRCm39) |
E465G |
probably damaging |
Het |
|
Other mutations in Crb1 |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL00593:Crb1
|
APN |
1 |
139,250,983 (GRCm39) |
missense |
probably benign |
0.16 |
IGL01591:Crb1
|
APN |
1 |
139,165,077 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL01644:Crb1
|
APN |
1 |
139,165,368 (GRCm39) |
nonsense |
probably null |
|
IGL01769:Crb1
|
APN |
1 |
139,264,806 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL02172:Crb1
|
APN |
1 |
139,164,965 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL02294:Crb1
|
APN |
1 |
139,162,520 (GRCm39) |
missense |
possibly damaging |
0.89 |
IGL02382:Crb1
|
APN |
1 |
139,165,352 (GRCm39) |
missense |
probably damaging |
0.99 |
IGL02411:Crb1
|
APN |
1 |
139,176,213 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL03070:Crb1
|
APN |
1 |
139,168,996 (GRCm39) |
missense |
possibly damaging |
0.79 |
IGL02984:Crb1
|
UTSW |
1 |
139,164,824 (GRCm39) |
frame shift |
probably null |
|
IGL02988:Crb1
|
UTSW |
1 |
139,164,824 (GRCm39) |
frame shift |
probably null |
|
IGL02991:Crb1
|
UTSW |
1 |
139,164,824 (GRCm39) |
frame shift |
probably null |
|
IGL02991:Crb1
|
UTSW |
1 |
139,164,822 (GRCm39) |
frame shift |
probably null |
|
IGL03014:Crb1
|
UTSW |
1 |
139,164,824 (GRCm39) |
frame shift |
probably null |
|
IGL03050:Crb1
|
UTSW |
1 |
139,164,824 (GRCm39) |
frame shift |
probably null |
|
IGL03054:Crb1
|
UTSW |
1 |
139,164,824 (GRCm39) |
frame shift |
probably null |
|
IGL03055:Crb1
|
UTSW |
1 |
139,164,824 (GRCm39) |
frame shift |
probably null |
|
IGL03097:Crb1
|
UTSW |
1 |
139,164,824 (GRCm39) |
frame shift |
probably null |
|
IGL03098:Crb1
|
UTSW |
1 |
139,164,824 (GRCm39) |
frame shift |
probably null |
|
IGL03134:Crb1
|
UTSW |
1 |
139,164,824 (GRCm39) |
frame shift |
probably null |
|
IGL03138:Crb1
|
UTSW |
1 |
139,164,824 (GRCm39) |
frame shift |
probably null |
|
IGL03147:Crb1
|
UTSW |
1 |
139,164,824 (GRCm39) |
frame shift |
probably null |
|
R0276:Crb1
|
UTSW |
1 |
139,251,073 (GRCm39) |
missense |
possibly damaging |
0.85 |
R0325:Crb1
|
UTSW |
1 |
139,168,904 (GRCm39) |
missense |
probably damaging |
1.00 |
R0401:Crb1
|
UTSW |
1 |
139,126,529 (GRCm39) |
splice site |
probably benign |
|
R0479:Crb1
|
UTSW |
1 |
139,126,352 (GRCm39) |
missense |
probably damaging |
0.98 |
R0734:Crb1
|
UTSW |
1 |
139,264,822 (GRCm39) |
missense |
probably benign |
0.25 |
R1573:Crb1
|
UTSW |
1 |
139,265,344 (GRCm39) |
missense |
probably damaging |
1.00 |
R1728:Crb1
|
UTSW |
1 |
139,168,876 (GRCm39) |
missense |
probably damaging |
1.00 |
R1728:Crb1
|
UTSW |
1 |
139,170,733 (GRCm39) |
missense |
probably damaging |
1.00 |
R1728:Crb1
|
UTSW |
1 |
139,171,155 (GRCm39) |
missense |
probably benign |
0.00 |
R1728:Crb1
|
UTSW |
1 |
139,162,517 (GRCm39) |
missense |
probably benign |
|
R1728:Crb1
|
UTSW |
1 |
139,165,360 (GRCm39) |
missense |
probably benign |
0.00 |
R1729:Crb1
|
UTSW |
1 |
139,168,876 (GRCm39) |
missense |
probably damaging |
1.00 |
R1729:Crb1
|
UTSW |
1 |
139,170,733 (GRCm39) |
missense |
probably damaging |
1.00 |
R1729:Crb1
|
UTSW |
1 |
139,171,155 (GRCm39) |
missense |
probably benign |
0.00 |
R1729:Crb1
|
UTSW |
1 |
139,162,517 (GRCm39) |
missense |
probably benign |
|
R1729:Crb1
|
UTSW |
1 |
139,165,360 (GRCm39) |
missense |
probably benign |
0.00 |
R1730:Crb1
|
UTSW |
1 |
139,168,876 (GRCm39) |
missense |
probably damaging |
1.00 |
R1730:Crb1
|
UTSW |
1 |
139,170,733 (GRCm39) |
missense |
probably damaging |
1.00 |
R1730:Crb1
|
UTSW |
1 |
139,171,155 (GRCm39) |
missense |
probably benign |
0.00 |
R1730:Crb1
|
UTSW |
1 |
139,162,517 (GRCm39) |
missense |
probably benign |
|
R1730:Crb1
|
UTSW |
1 |
139,165,360 (GRCm39) |
missense |
probably benign |
0.00 |
R1739:Crb1
|
UTSW |
1 |
139,165,360 (GRCm39) |
missense |
probably benign |
0.00 |
R1739:Crb1
|
UTSW |
1 |
139,168,876 (GRCm39) |
missense |
probably damaging |
1.00 |
R1739:Crb1
|
UTSW |
1 |
139,170,733 (GRCm39) |
missense |
probably damaging |
1.00 |
R1739:Crb1
|
UTSW |
1 |
139,171,155 (GRCm39) |
missense |
probably benign |
0.00 |
R1739:Crb1
|
UTSW |
1 |
139,162,517 (GRCm39) |
missense |
probably benign |
|
R1762:Crb1
|
UTSW |
1 |
139,165,360 (GRCm39) |
missense |
probably benign |
0.00 |
R1762:Crb1
|
UTSW |
1 |
139,168,876 (GRCm39) |
missense |
probably damaging |
1.00 |
R1762:Crb1
|
UTSW |
1 |
139,170,733 (GRCm39) |
missense |
probably damaging |
1.00 |
R1762:Crb1
|
UTSW |
1 |
139,171,155 (GRCm39) |
missense |
probably benign |
0.00 |
R1762:Crb1
|
UTSW |
1 |
139,162,517 (GRCm39) |
missense |
probably benign |
|
R1762:Crb1
|
UTSW |
1 |
139,165,269 (GRCm39) |
missense |
probably damaging |
1.00 |
R1783:Crb1
|
UTSW |
1 |
139,170,733 (GRCm39) |
missense |
probably damaging |
1.00 |
R1783:Crb1
|
UTSW |
1 |
139,171,155 (GRCm39) |
missense |
probably benign |
0.00 |
R1783:Crb1
|
UTSW |
1 |
139,162,517 (GRCm39) |
missense |
probably benign |
|
R1783:Crb1
|
UTSW |
1 |
139,165,360 (GRCm39) |
missense |
probably benign |
0.00 |
R1783:Crb1
|
UTSW |
1 |
139,168,876 (GRCm39) |
missense |
probably damaging |
1.00 |
R1784:Crb1
|
UTSW |
1 |
139,170,733 (GRCm39) |
missense |
probably damaging |
1.00 |
R1784:Crb1
|
UTSW |
1 |
139,171,155 (GRCm39) |
missense |
probably benign |
0.00 |
R1784:Crb1
|
UTSW |
1 |
139,162,517 (GRCm39) |
missense |
probably benign |
|
R1784:Crb1
|
UTSW |
1 |
139,165,360 (GRCm39) |
missense |
probably benign |
0.00 |
R1784:Crb1
|
UTSW |
1 |
139,168,876 (GRCm39) |
missense |
probably damaging |
1.00 |
R1785:Crb1
|
UTSW |
1 |
139,170,733 (GRCm39) |
missense |
probably damaging |
1.00 |
R1785:Crb1
|
UTSW |
1 |
139,171,155 (GRCm39) |
missense |
probably benign |
0.00 |
R1785:Crb1
|
UTSW |
1 |
139,162,517 (GRCm39) |
missense |
probably benign |
|
R1785:Crb1
|
UTSW |
1 |
139,165,360 (GRCm39) |
missense |
probably benign |
0.00 |
R1785:Crb1
|
UTSW |
1 |
139,168,876 (GRCm39) |
missense |
probably damaging |
1.00 |
R1848:Crb1
|
UTSW |
1 |
139,164,750 (GRCm39) |
missense |
probably damaging |
0.97 |
R1894:Crb1
|
UTSW |
1 |
139,170,931 (GRCm39) |
missense |
probably benign |
0.02 |
R2057:Crb1
|
UTSW |
1 |
139,242,488 (GRCm39) |
missense |
probably damaging |
1.00 |
R2136:Crb1
|
UTSW |
1 |
139,265,163 (GRCm39) |
missense |
probably benign |
0.03 |
R2140:Crb1
|
UTSW |
1 |
139,164,750 (GRCm39) |
missense |
probably benign |
0.01 |
R2363:Crb1
|
UTSW |
1 |
139,265,016 (GRCm39) |
missense |
possibly damaging |
0.89 |
R3605:Crb1
|
UTSW |
1 |
139,165,077 (GRCm39) |
missense |
probably damaging |
1.00 |
R3817:Crb1
|
UTSW |
1 |
139,175,835 (GRCm39) |
missense |
probably benign |
|
R3942:Crb1
|
UTSW |
1 |
139,265,211 (GRCm39) |
missense |
possibly damaging |
0.49 |
R4272:Crb1
|
UTSW |
1 |
139,251,049 (GRCm39) |
missense |
probably benign |
0.04 |
R4301:Crb1
|
UTSW |
1 |
139,176,568 (GRCm39) |
missense |
probably benign |
0.01 |
R4403:Crb1
|
UTSW |
1 |
139,176,117 (GRCm39) |
missense |
probably benign |
0.00 |
R4700:Crb1
|
UTSW |
1 |
139,126,509 (GRCm39) |
missense |
probably damaging |
0.96 |
R4771:Crb1
|
UTSW |
1 |
139,255,942 (GRCm39) |
missense |
probably damaging |
1.00 |
R4845:Crb1
|
UTSW |
1 |
139,170,772 (GRCm39) |
missense |
probably benign |
0.06 |
R4867:Crb1
|
UTSW |
1 |
139,170,752 (GRCm39) |
missense |
probably damaging |
1.00 |
R5159:Crb1
|
UTSW |
1 |
139,170,756 (GRCm39) |
missense |
probably damaging |
0.99 |
R5270:Crb1
|
UTSW |
1 |
139,164,602 (GRCm39) |
missense |
probably damaging |
0.97 |
R5347:Crb1
|
UTSW |
1 |
139,265,109 (GRCm39) |
missense |
probably damaging |
1.00 |
R5513:Crb1
|
UTSW |
1 |
139,164,559 (GRCm39) |
critical splice donor site |
probably null |
|
R5641:Crb1
|
UTSW |
1 |
139,176,627 (GRCm39) |
missense |
probably damaging |
0.99 |
R5754:Crb1
|
UTSW |
1 |
139,159,337 (GRCm39) |
missense |
probably damaging |
1.00 |
R5968:Crb1
|
UTSW |
1 |
139,170,739 (GRCm39) |
missense |
probably damaging |
1.00 |
R6122:Crb1
|
UTSW |
1 |
139,176,686 (GRCm39) |
nonsense |
probably null |
|
R6369:Crb1
|
UTSW |
1 |
139,165,200 (GRCm39) |
missense |
probably damaging |
1.00 |
R6809:Crb1
|
UTSW |
1 |
139,170,864 (GRCm39) |
missense |
probably benign |
0.00 |
R7020:Crb1
|
UTSW |
1 |
139,159,341 (GRCm39) |
missense |
possibly damaging |
0.85 |
R7072:Crb1
|
UTSW |
1 |
139,165,013 (GRCm39) |
missense |
probably damaging |
1.00 |
R7073:Crb1
|
UTSW |
1 |
139,176,049 (GRCm39) |
missense |
probably damaging |
0.99 |
R7135:Crb1
|
UTSW |
1 |
139,171,105 (GRCm39) |
missense |
probably damaging |
0.97 |
R7493:Crb1
|
UTSW |
1 |
139,164,768 (GRCm39) |
missense |
probably damaging |
1.00 |
R7539:Crb1
|
UTSW |
1 |
139,175,967 (GRCm39) |
missense |
probably damaging |
1.00 |
R7554:Crb1
|
UTSW |
1 |
139,265,019 (GRCm39) |
missense |
probably damaging |
1.00 |
R7593:Crb1
|
UTSW |
1 |
139,164,978 (GRCm39) |
missense |
probably damaging |
1.00 |
R7740:Crb1
|
UTSW |
1 |
139,165,428 (GRCm39) |
missense |
probably benign |
0.01 |
R7912:Crb1
|
UTSW |
1 |
139,170,909 (GRCm39) |
missense |
probably damaging |
1.00 |
R8036:Crb1
|
UTSW |
1 |
139,165,122 (GRCm39) |
missense |
probably benign |
0.07 |
R8042:Crb1
|
UTSW |
1 |
139,242,392 (GRCm39) |
missense |
probably damaging |
0.99 |
R8329:Crb1
|
UTSW |
1 |
139,165,005 (GRCm39) |
missense |
probably damaging |
1.00 |
R8332:Crb1
|
UTSW |
1 |
139,165,152 (GRCm39) |
missense |
probably damaging |
0.96 |
R8880:Crb1
|
UTSW |
1 |
139,164,886 (GRCm39) |
missense |
probably benign |
0.19 |
R8894:Crb1
|
UTSW |
1 |
139,175,750 (GRCm39) |
missense |
possibly damaging |
0.95 |
R9052:Crb1
|
UTSW |
1 |
139,171,161 (GRCm39) |
missense |
possibly damaging |
0.50 |
R9138:Crb1
|
UTSW |
1 |
139,162,468 (GRCm39) |
missense |
|
|
R9209:Crb1
|
UTSW |
1 |
139,171,051 (GRCm39) |
missense |
probably damaging |
0.98 |
R9567:Crb1
|
UTSW |
1 |
139,171,208 (GRCm39) |
missense |
probably benign |
0.04 |
X0066:Crb1
|
UTSW |
1 |
139,175,983 (GRCm39) |
missense |
probably benign |
0.10 |
Z1176:Crb1
|
UTSW |
1 |
139,164,824 (GRCm39) |
frame shift |
probably null |
|
Z1177:Crb1
|
UTSW |
1 |
139,264,766 (GRCm39) |
critical splice donor site |
probably null |
|
Z1177:Crb1
|
UTSW |
1 |
139,176,639 (GRCm39) |
missense |
possibly damaging |
0.80 |
Z1177:Crb1
|
UTSW |
1 |
139,164,824 (GRCm39) |
frame shift |
probably null |
|
|
Protein Function and Prediction |
CRB1 is a homologue to Drosophila Crumbs, a protein that establishes apico-basal polarity in ectoderm-derived epithelia (1). Crb1 is proposed to function in cell-cell interaction and in the maintenance of cell polarity in the retina (2). The Drosophila homologue of CRB1, crumbs, is involved in the morphogenesis of the photoreceptors of the retina (3). Crumbs is also a part of a scaffold that controls zonula adherens assembly and defines the stalk as an apical membrane subdomain (3).
|
Expression/Localization |
Northern blot analysis detected the CRB1 transcript in neural retina; RT-PCR detected CRB1 in adult and fetal brain (2). In situ hybridization of mouse tissues determined that Crb1 is expressed exclusively in the eye and the brain; in post-natal stages, Crb1 is strongly detected in photoreceptor cells (4).
|
Background |
Mutations in CRB1 are associated with retinal phenotypes (Table 1).
Table 1. Phenotypes associated with mutations in CRB1.
Phenotype
|
MIM Number
|
Description
|
Refs
|
Leber congenital amaurosis 8
|
613835
|
Early-onset childhood retinal dystrophies characterized by vision loss, nystagmus, and severe retinal dysfunction
|
(5;6)
|
Pigmented paravenous chorioretinal atrophy
|
172870
|
Stationary disease of the ocular fundus in which bone corpuscle pigmentation is seen in a paravenous distribution; patients are usually asymptomatic
|
(7)
|
Retinitis pigmentosa-12, autosomal recessive
|
600105
|
Progressive retinal degeneration; symptoms include night blindness, the development of tunnel vision, slowly progressive decreased central vision starting at approximately 20 years of age, decreased visual acuity, constricted visual fields, dyschromatopsia, and dark pigmentary clumps in the midperiphery and perivenous areas ('bone spicules'), attenuated retinal vessels, cystoid macular edema, fine pigmented vitreous cells, and waxy optic disc pallor
|
(2)
|
Crb1tm1Wij/tm1Wij; MGI: 3052072
involves: 129P2/OlaHsd * C57BL/6
In homozygotes, light exposure accelerates retinal degeneration (8). Retinal degeneration is observable by 3 months (8). Also, photoreceptor cells form half rosettes and double layers that rupture outer membrane layer and protrude into interphotoreceptor space (8).
Crb1rd8/rd8; MGI:2676366
STOCK Crb1rd8/J
Homozygous mice have irregularly shaped spots concentrated in the inferior nasal quadrant of the fundus as early as week 3 that correspond to retinal folds and pseudorosettes, retinal thinning, abnormal Muller cell morphology, breakdown of the photoreceptor lamellae, decreased photoreceptor cell number, swelling and disorder of the photoreceptor inner segments, and degeneration of the photoreceptor outer segments by week 10 (9).
Crb1rd8/rd8; MGI:2676366
involves: C57BL/6N
Homozygotes in this genetic background have retinal pigment epithelium vacuolation, retinal lesions and spots, and diffuse lesions by 6 weeks (10).
Crb1rd8/rd8; MGI:2676366
B6.Cg-Crb1rd8
In this genetic background, mice do not display the spotting phenotype when backcrossed from a CAST/EiJ background onto a C57BL/6 background (9).
Crb1rd8/rd8; MGI:2676366
involves: C3HfB6/Ga * C57BL/6 * CAST/EiJ
In this genetic background, 19% of mice do not display the spotting phenotype on a CAST/EiJ mixed background (9).
|
References |
2. den Hollander, A. I., ten Brink, J. B., de Kok, Y. J., van Soest, S., van den Born, L. I., van Driel, M. A., van de Pol, D. J., Payne, A. M., Bhattacharya, S. S., Kellner, U., Hoyng, C. B., Westerveld, A., Brunner, H. G., Bleeker-Wagemakers, E. M., Deutman, A. F., Heckenlively, J. R., Cremers, F. P., and Bergen, A. A. (1999) Mutations in a Human Homologue of Drosophila Crumbs Cause Retinitis Pigmentosa (RP12). Nat Genet. 23, 217-221.
3. Pellikka, M., Tanentzapf, G., Pinto, M., Smith, C., McGlade, C. J., Ready, D. F., and Tepass, U. (2002) Crumbs, the Drosophila Homologue of Human CRB1/RP12, is Essential for Photoreceptor Morphogenesis. Nature. 416, 143-149.
4. den Hollander, A. I., Ghiani, M., de Kok, Y. J., Wijnholds, J., Ballabio, A., Cremers, F. P., and Broccoli, V. (2002) Isolation of Crb1, a Mouse Homologue of Drosophila Crumbs, and Analysis of its Expression Pattern in Eye and Brain. Mech Dev. 110, 203-207.
5. Henderson, R. H., Mackay, D. S., Li, Z., Moradi, P., Sergouniotis, P., Russell-Eggitt, I., Thompson, D. A., Robson, A. G., Holder, G. E., Webster, A. R., and Moore, A. T. (2011) Phenotypic Variability in Patients with Retinal Dystrophies due to Mutations in CRB1. Br J Ophthalmol. 95, 811-817.
6. Lotery, A. J., Jacobson, S. G., Fishman, G. A., Weleber, R. G., Fulton, A. B., Namperumalsamy, P., Heon, E., Levin, A. V., Grover, S., Rosenow, J. R., Kopp, K. K., Sheffield, V. C., and Stone, E. M. (2001) Mutations in the CRB1 Gene Cause Leber Congenital Amaurosis. Arch Ophthalmol. 119, 415-420.
7. McKay, G. J., Clarke, S., Davis, J. A., Simpson, D. A., and Silvestri, G. (2005) Pigmented Paravenous Chorioretinal Atrophy is Associated with a Mutation within the Crumbs Homolog 1 (CRB1) Gene. Invest Ophthalmol Vis Sci. 46, 322-328.
8. van de Pavert, S. A., Kantardzhieva, A., Malysheva, A., Meuleman, J., Versteeg, I., Levelt, C., Klooster, J., Geiger, S., Seeliger, M. W., Rashbass, P., Le Bivic, A., and Wijnholds, J. (2004) Crumbs Homologue 1 is Required for Maintenance of Photoreceptor Cell Polarization and Adhesion during Light Exposure. J Cell Sci. 117, 4169-4177.
9. Mehalow, A. K., Kameya, S., Smith, R. S., Hawes, N. L., Denegre, J. M., Young, J. A., Bechtold, L., Haider, N. B., Tepass, U., Heckenlively, J. R., Chang, B., Naggert, J. K., and Nishina, P. M. (2003) CRB1 is Essential for External Limiting Membrane Integrity and Photoreceptor Morphogenesis in the Mammalian Retina. Hum Mol Genet. 12, 2179-2189.
10. Mattapallil, M. J., Wawrousek, E. F., Chan, C. C., Zhao, H., Roychoudhury, J., Ferguson, T. A., and Caspi, R. R. (2012) The Rd8 Mutation of the Crb1 Gene is Present in Vendor Lines of C57BL/6N Mice and Embryonic Stem Cells, and Confounds Ocular Induced Mutant Phenotypes. Invest Ophthalmol Vis Sci. 53, 2921-2927.
|
Posted On |
2012-10-29 |
Science Writer |
Anne Murray |