|Coordinate||56,414,431 bp (GRCm38)|
|Base Change||T ⇒ A (forward strand)|
|Gene Name||oculocutaneous albinism II|
|Synonym(s)||D7H15S12, p, D7H15S12|
|Chromosomal Location||56,239,760-56,536,518 bp (+)|
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]
|Amino Acid Change||Tryptophan changed to Arginine|
|Institutional Source||Beutler Lab|
|Gene Model||not available|
AA Change: W725R
|Predicted Effect||probably damaging
PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
|Predicted Effect||probably benign|
|Predicted Effect||probably benign|
|Meta Mutation Damage Score||Not available|
|Is this an essential gene?||Probably nonessential (E-score: 0.235)|
|Candidate Explorer Status||CE: no linkage results|
Linkage Analysis Data
|Alleles Listed at MGI|
|Mode of Inheritance||Autosomal Recessive|
|Last Updated||2018-01-12 4:38 PM by Diantha La Vine|
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.
The mutated nucleotide is indicated in red lettering and results in a tryptophan to arginine change at amino acid 725 in the OCA2 protein.
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.
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.|
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
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.
1. Rinchik, E. M., Bultman, S. J., Horsthemke, B., Lee, S. T., Strunk, K. M., Spritz, R. A., Avidano, K. M., Jong, M. T., and Nicholls, R. D. (1993) A gene for the mouse pink-eyed dilution locus and for human type II oculocutaneous albinism, Nature 361, 72-76.
|Science Writers||Nora G. Smart|
|Illustrators||Diantha La Vine|
|Authors||Sophie Rutschmann, Bruce Beutler|