|Coordinate||56,423,352 bp (GRCm38)|
|Base Change||A ⇒ T (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||Tyrosine changed to Phenylalanine|
|Institutional Source||Beutler Lab|
|Gene Model||predicted gene model for protein(s): [ENSMUSP00000032633] [ENSMUSP00000119529] [ENSMUSP00000119099]|
AA Change: Y765F
|Predicted Effect||probably benign
PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)
|Predicted Effect||probably benign|
|Predicted Effect||probably benign|
|Meta Mutation Damage Score||0.66|
|Is this an essential gene?||Probably nonessential (E-score: 0.235)|
|Candidate Explorer Status||CE: good candidate; human score: -1; ML prob: 0.548|
Linkage Analysis Data
|Alleles Listed at MGI|
|Mode of Inheritance||Autosomal Recessive|
|Local Stock||Live Mice|
|Last Updated||2018-01-12 4:39 PM by Diantha La Vine|
|Record Created||2013-05-24 7:09 PM by Tiana Purrington|
The draco1 phenotype was identified among N-ethyl-N-nitrosourea (ENU)-induced G3 mice of the pedigree R0440, some of which exhibited a light gray coat and red eyes (Figure 1). Other phenotypes associated with Oca2 mutations such as slight susceptibility to L. monocytogenes (see the records for charbon and quicksilver) have not been examined in draco1 mice.
|Nature of Mutation|
Whole exome HiSeq sequencing of the G1 grandsire identified 68 mutations. The pigmentation phenotype of the coat and eyes was linked to a mutation in Oca2: an A to T transversion at base pair 56,423,352 (v38) on chromosome 7, or base pair 183,760 in the GenBank genomic region NC_000073 encoding Oca2. Linkage was found with a recessive model of inheritance (P = 9.776 x 10-6), wherein 6 affected mice were homozygous (N = 5) or heterozygous (N = 1) for the variant allele, and 18 unaffected mice were either heterozygous (N = 12) or homozygous for the reference allele (N = 6) (Figure 2). The mutation corresponds to residue 2,424 in the NM_021879 mRNA sequence in exon 22 of 24 total exons.
The mutated nucleotide is indicated in red. The mutation results in a tyrosine (Y) to phenylalanine (F) substitution at residue 765 in the OCA2 protein.
The draco1 mutation occurs within transmembrane domain 11 of 12 total transmembrane domains of the OCA2 protein (Figure 3). Protein expression and localization of OCA2 has not been examined in the draco1 mice.
Please see the record quicksilver for information about Oca2.
The draco1 mutation results in an amino acid change (Y765F) within transmembrane domain 11, a region of OCA2 that is highly conserved between mouse and human OCA2; the function of this region is unknown. Mutations in Oca2 are known to cause a variable 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). For example, mice with null alleles of Oca2 have very little to no eumelanin in their coat and eyes, resulting in a hypopigmentation phenotype: light grey fur with pink eyes on a nonagouti background (e.g., C57BL/6J), and cream-colored mice on an agouti background (3;4). The null mice have a reduced number of very small eumelanosomes in pigmented tissue with a concomitant decrease in the expression levels of melanosomal proteins (e.g., tyrosinase; see the record for ghost). The light coat color of draco1 mice suggests a reduced function of the OCA2 protein in these animals.
draco1(F):5'- AAGGTTCTTTAGGTTTCGTAAATCAGTCACA -3'
draco1(R):5'- CAGTTTTCTTTAGACTTCAGTCCCAGCA -3'
draco1_seq(F):5'- TTCGTAAATCAGTCACAGTGGG -3'
draco1_seq(R):5'- cccagagaccccagacc -3'
Draco1 genotyping is performed by amplifying the region containing the mutation using PCR, followed by sequencing of the amplified region to detect the single nucleotide transversion.
Draco1(F): 5’- AAGGTTCTTTAGGTTTCGTAAATCAGTCACA- 3’
Draco1(R): 5’- CAGTTTTCTTTAGACTTCAGTCCCAGCA- 3’
Draco1_seq(F): 5’- TTCGTAAATCAGTCACAGTGGG -3’
1) 94°C 2:00
2) 94°C 0:30
3) 55°C 0:30
4) 72°C 1:00
5) repeat steps (2-4) 40X
6) 72°C 10:00
7) 4°C ∞
The following sequence of 983 nucleotides (from Genbank genomic region NC_000073 for linear DNA sequence of Oca2) is amplified:
183429 aa ggttctttag gtttcgtaaa tcagtcacag tgggtggctc ttataatttt
183481 ctatggcgtg tgtccataat actcgtttct tccacagatt cctgtactcc tgaacctgag
183541 ccaagaccct gaaattagtt tgcctgcact gcctctcatg tatgccctgg ccctcggtgc
183601 ctgcctggga ggtaagggtt gccgactgca ttttgggaga ccacactaac ctcgttgtct
183661 agacaaagca agatttagta gttaacagat caaaagtaaa ttgaggagaa tcctggagac
183721 ttcctgattt caaaatctga acaaccagaa ctcctcagtt cctctgtgaa gcctctcctt
183781 ttggtcataa cctttcatgg attgggtccc agaaccctaa tcacggctac ccagggaaat
183841 gaagaaatgg aaaaaccatg gacatacagg aaaattggga tcatgtggtc tggggtctct
183901 gggaagctca gagtttatta tatgcagttg aacagggagg tgaggttatt tcatacatct
183961 gaccaagaag acaggcttag ctaatctctg taggagcggt ctctgtaggg gagcagtctt
184021 caggctgtaa acacacaggg gggggggggg ggaagctata acagacatct gctttacaca
184081 ctgtctccac tcacacccag atcagaggaa ggctttgcta cagcaacaat atagtcactc
184141 aggatttcac tttctcccta tttctcactc tacttctcac tctgcagaac ccatgatctg
184201 atgacagtca ctgttaatag ttcaaagcta atgcattccc accctgtcca agtaaggctc
184261 tgcaatggac attctttctc attctcctct ctgggctccc ctgttcagaa ggaatgcaca
184321 tgcattaggt agagcaggga ctctatcgca aaggaagagg gatggtaaga gatcaagcac
184381 aggtgctggg actgaagtct aaagaaaact g
Primer binding sites are underlined and the sequencing primer is highlighted; the mutated nucleotide 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.
2. RUSSELL, E. S. (1949) A Quantitative Histological Study of the Pigment found in the Coat-Color Mutants of the House Mouse; the Nature of the Effects of Genic Substitution in Five Major Allelic Series. Genetics. 34, 146-166.
3. Silvers, W. K. (Ed.) (1979) The Coat Colors of Mice: a Model for Mammalian Gene Action and Interaction. Springer-Verlag.
|Science Writers||Anne Murray|