Phenotypic Mutation 'whitemouse' (pdf version)
Allelewhitemouse
Mutation Type missense
Chromosome7
Coordinate56,064,179 bp (GRCm39)
Base Change T ⇒ A (forward strand)
Gene Oca2
Gene Name oculocutaneous albinism II
Synonym(s) p, D7H15S12, D7H15S12
Chromosomal Location 55,889,508-56,186,266 bp (+) (GRCm39)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the human homolog of the mouse p (pink-eyed dilution) gene. The encoded protein is believed to be an integral membrane protein involved in small molecule transport, specifically tyrosine, which is a precursor to melanin synthesis. It is involved in mammalian pigmentation, where it may control skin color variation and act as a determinant of brown or blue eye color. Mutations in this gene result in type 2 oculocutaneous albinism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
PHENOTYPE: Mutations generally result in varying degrees of coat and eye pigment dilution. Specific alleles produce cleft palate, reproductive, endocrine or neurological disorders, and/or lethality. [provided by MGI curators]
Accession Number
NCBI RefSeq: NM_021879; MGI: 97454
MappedYes 
Amino Acid Change Tryptophan changed to Arginine
Institutional SourceBeutler Lab
Gene Model not available
AlphaFold Q62052
SMART Domains Protein: ENSMUSP00000032633
Gene: ENSMUSG00000030450
AA Change: W725R

DomainStartEndE-ValueType
transmembrane domain 171 193 N/A INTRINSIC
Pfam:ArsB 319 558 2e-10 PFAM
Pfam:CitMHS 337 770 2e-49 PFAM
Pfam:ArsB 562 827 8.9e-9 PFAM
Pfam:Na_sulph_symp 573 832 6e-13 PFAM
Predicted Effect probably damaging

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
(Using ENSMUST00000032633)
Predicted Effect probably benign
SMART Domains Protein: ENSMUSP00000119099
Gene: ENSMUSG00000030450

DomainStartEndE-ValueType
transmembrane domain 171 193 N/A INTRINSIC
Predicted Effect probably benign
Meta Mutation Damage Score Not available question?
Is this an essential gene? Probably nonessential (E-score: 0.106) question?
Phenotypic Category Autosomal Recessive
Candidate Explorer Status loading ...
Single pedigree
Linkage Analysis Data
Penetrance 100 % 
Alleles Listed at MGI
All alleles(66) : Gene trapped(1) Spontaneous(19) Chemically induced(7) Radiation induced(39)
Lab Alleles
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00509:Oca2 APN 7 55930594 missense probably damaging 0.99
IGL01022:Oca2 APN 7 55974504 missense probably damaging 1.00
IGL01666:Oca2 APN 7 55964559 splice site probably null
IGL02157:Oca2 APN 7 55974545 splice site probably null
IGL02213:Oca2 APN 7 55971232 splice site probably benign
IGL02314:Oca2 APN 7 56006899 missense probably benign 0.00
IGL03083:Oca2 APN 7 55945232 missense probably benign 0.28
IGL03356:Oca2 APN 7 56185716 missense probably benign 0.01
charbon UTSW 7 55966153 missense probably damaging 1.00
cotton UTSW 7 56185716 missense probably benign 0.00
cutworm UTSW 7 55966168 missense probably damaging 1.00
Dirk UTSW 7 56185716 missense probably benign 0.00
draco1 UTSW 7 56073100 missense probably benign 0.00
faded UTSW 7 55974409 missense probably benign 0.19
hardy UTSW 7 55945208 missense probably damaging 1.00
narwhal UTSW 7 55945246 nonsense probably null
quicksilver UTSW 7 55974409 missense probably benign 0.19
renesmee UTSW 7 56185716 missense probably benign 0.00
slush UTSW 7 55927189 critical splice donor site probably null
snowflake UTSW 7 55974428 missense probably damaging 1.00
R0440:Oca2 UTSW 7 56073100 missense probably benign 0.00
R1067:Oca2 UTSW 7 55966141 missense probably damaging 1.00
R1349:Oca2 UTSW 7 56185716 missense probably benign 0.00
R1372:Oca2 UTSW 7 56185716 missense probably benign 0.00
R1457:Oca2 UTSW 7 55971269 missense probably damaging 1.00
R1737:Oca2 UTSW 7 55978533 missense probably damaging 1.00
R1802:Oca2 UTSW 7 55904728 missense possibly damaging 0.96
R1957:Oca2 UTSW 7 55971246 missense possibly damaging 0.82
R1966:Oca2 UTSW 7 56064215 missense probably damaging 0.99
R2082:Oca2 UTSW 7 55946885 missense probably benign 0.01
R2229:Oca2 UTSW 7 56006903 missense probably benign 0.11
R4120:Oca2 UTSW 7 55904630 missense probably damaging 1.00
R4192:Oca2 UTSW 7 55946997 missense probably damaging 1.00
R4405:Oca2 UTSW 7 56064182 missense possibly damaging 0.63
R4654:Oca2 UTSW 7 55978560 missense probably benign 0.44
R4701:Oca2 UTSW 7 55904750 missense probably benign 0.00
R4887:Oca2 UTSW 7 55980106 nonsense probably null
R5053:Oca2 UTSW 7 55973328 missense probably benign 0.02
R5215:Oca2 UTSW 7 55945246 nonsense probably null
R5430:Oca2 UTSW 7 55945208 missense probably damaging 1.00
R5677:Oca2 UTSW 7 56064210 missense probably damaging 1.00
R6416:Oca2 UTSW 7 55978515 missense probably benign 0.44
R6645:Oca2 UTSW 7 55964522 missense probably benign 0.21
R7257:Oca2 UTSW 7 55929286 intron probably benign
R7409:Oca2 UTSW 7 56064145 missense probably benign 0.00
R7530:Oca2 UTSW 7 55981720 missense probably damaging 0.99
R7820:Oca2 UTSW 7 55981713 missense probably damaging 1.00
R9043:Oca2 UTSW 7 55927189 critical splice donor site probably null
R9153:Oca2 UTSW 7 55943586 missense probably benign 0.00
R9205:Oca2 UTSW 7 55966168 missense probably damaging 1.00
R9681:Oca2 UTSW 7 55943623 missense probably null 1.00
Z1088:Oca2 UTSW 7 55980123 missense probably null 0.83
Mode of Inheritance Autosomal Recessive
Local Stock Embryos
Repository

none

Last Updated 2018-01-12 4:38 PM by Diantha La Vine
Record Created unknown
Record Posted 2008-04-10
Phenotypic Description
The whitemouse mutation was induced by an N-ethyl-N-nitrosourea (ENU)-mutagenesis on a C57BL/6J (black) background and was discovered in G3 animals.  Whitemouse is a strictly recessive phenotype with a light coat color and ocular albinism, similar to the phenotype created by mutations at the Oca2 or p (pink-eyed dilution) locus.  Mutations at Oca2 are known to cause a reduction of eumelanin (black-brown) pigment and altered morphology of black pigment granules (eumelanosomes), but have little effect on pheomelanin (yellow-red) pigment (1;2).
 
Due to a high resemblance in their phenotypes, snowflake and whitemouse mutants were tested for allelism and found to be allelic.  Since both mutations mapped to Chromosome 7, and are similar to classical p locus phenotypes, sequencing of the p locus was undertaken at the genomic level and the causative mutation was identified for both snowflake and whitemouse mutants.
Nature of Mutation
The whitemouse mutation was mapped to Chromosome 7, and corresponds to a T to A transversion at position 2303 of the Oca2 transcript, in exon 21 of 24 total exons. 
 
2288 ATTGTCCTGATAGTGTGGGTCTCAGCCTTGGCA
720  -I--V--L--I--V--W--V--S--A--L--A-
 
The mutated nucleotide is indicated in red lettering and results in a tryptophan to arginine change at amino acid 725 in the OCA2 protein.
Illustration of Mutations in
Gene & Protein
Protein Prediction
Figure 1. Domain organization and function of the OCA2 protein. A, Topography. B, Domain structure. The whitemouse mutation results in a tryptophan to arginine change at amino acid 725 in the OCA2 protein. Other mutations found in OCA2  are noted in red. This image is interactive. Click on the mutations for more specific information.

The whitemouse mutation occurs in the tenth transmembrane domain of the OCA2 protein (Figure 1).  It is unknown whether normal levels of the altered OCA2 protein exist in whitemouse mice or whether this protein is localized appropriately.

 
Please see the record for quicksilver for information about Oca2.
Putative Mechanism
The whitemouse mutation substitutes a polar, highly basic arginine for nonpolar, neutral tryptophan at amino acid 725 of the OCA2 protein.  This substitution occurs at a residue conserved between mouse and human in the tenth transmembrane region.  Arginine can form multiple hydrogen bonds and can be methylated, unlike tryptophan which contains an indole functional group.  Presumably, the substitution of a neutral, nonpolar hydrophobic residue with highly basic arginine interferes with the formation of the tenth transmembrane region and the function of the OCA2 protein.  Human mutations in the same region cause oculocutaneous albinism II (OCA2, OMIM #203200).  The lighter coat color of snowflake and whitemouse mutants suggest that the mutations present in these animals more severely impair OCA2 protein function than the mutations present in the darker quicksilver, faded, or charbon mice.
 
For a further explanation of the whitemouse mutant phenotype, please refer to the record for quicksilver.
Primers Primers cannot be located by automatic search.
Genotyping
Whitemouse genotyping is performed by amplifying the region containing the mutation using PCR, followed by sequencing of the amplified region to detect the single nucleotide change.
 
Primers for PCR amplification
White(F): 5’-AGCACTGACGGGAGCCTACTTTAC-3’
White(R): 5’-CTCTAAGCACTCTTTGGCCCTGAAC-3’
 
PCR program
1) 94°C             2:00
2) 94°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               ∞
 
Primers for sequencing
White_seq(F): 5’- CAAGGTATAGGTATGGCCCTC-3’
White_seq(R): 5’- CAACAGAGGAGCTGGTTTCA-3’
 
The following sequence of 1181 nucleotides (from Genbank genomic region NC_000073 for linear DNA sequence of Oca2) is amplified:
 
174131            agcactgacg ggagcctact ttaccctggg taacctagag atgaagggga
174181 tacttgtcaa ataatataca attatagatg cttgctatct tgcttttgcc tttagttaca
174241 gtaagtctaa aaaggagtag cacatagtaa gtgaatgctg cagaaattcc catcttagga
174301 ttctgctggg ccaatctgtg tggtcatcag atgttagtaa gtaatgtaca tttttcctca
174361 catagagcta tttggctgag aatggctcct ctccagttac ttgtggccaa ggtataggta
174421 tggccctcat ttgcatatct atgcttacct gggtcttatc atgtatcaga agaaagagta
174481 acaatctttt gactcttttt gtgtatatgg tttagtattg cagtagttaa tgcataatgt
174541 ggctatcatc attttgtgta tatggtttag tattgcagta gttaatgcat aatgtggcta
174601 tcatcatttt agatggttcc agaagatcag cgctttgcag ctgccattgt cctgatagtg
174661 tgggtctcag ccttggcatc atccttgatt gacaacatcc catttactgc tacgatggta
174721 agtggtgtga tccgtgtgtt taaggccaag ctctacctgt tcctatctgg gctcatcctt
174781 tttctcccta agaagcaggg catgaaacca gctcctctgt tgcccttaca tgtaagggga
174841 aaatgtgagc agctggatac ggaacactta gcgaacagtt acaggctgga gaccaggctt
174901 tggagagtgg acagcatatc atggtcactg cctgtttggg gagcccagtt gagggctgct
174961 acccttccca gaaaaaaaaa aagtttcatt ttttttcaaa ggaaatacaa gaaaccaaaa
175021 gtctgagctg ttgccttcat ttttcctcaa atgcagaagt tatttattct aagcagcctg
175081 aatggattct ggtacttggc ctgtacatat agagatttaa gtctcctttt gattctaact
175141 cccaaccaac accaagaccc ctatctctgg gctatcttct tcgtcattga ttgtttgtct
175201 taggacagga actgtggtct ttggtgtgaa aaaaatcaaa gtgagaatag agatttaaag
175261 gtaagatctg agtcctgcca caaacagttc agggccaaag agtgcttaga g
 
PCR primer binding sites are underlined; sequencing primer binding sites are highlighted in gray; the mutated T is shown in red text.
References
Science Writers Nora G. Smart
Illustrators Diantha La Vine
AuthorsSophie Rutschmann, Bruce Beutler
Edit History
2011-01-07 9:36 AM (current)
2010-10-01 10:39 AM
2010-10-01 10:37 AM
2010-02-03 9:31 AM