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|Coordinate||56,316,405 bp (GRCm38)|
|Base Change||A ⇒ G (forward strand)|
|Gene Name||oculocutaneous albinism II|
|Synonym(s)||D7H15S12, p, D7H15S12|
|Chromosomal Location||56,239,760-56,536,517 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||Threonine changed to Alanine|
|Institutional Source||Beutler Lab|
T382A in Ensembl: ENSMUSP00000032633 (fasta)
|Gene Model||not available|
|Predicted Effect||probably damaging
PolyPhen 2 Score 0.997 (Sensitivity: 0.40; Specificity: 0.98)
|Phenotypic Category||Autosomal Recessive|
|Alleles Listed at MGI|
|Mode of Inheritance||Autosomal Recessive|
|Local Stock||Sperm, gDNA|
|Last Updated||2018-01-12 4:36 PM by Diantha La Vine|
The charbon mutation was induced by an N-ethyl-N-nitrosourea (ENU)-mutagenesis on a C57BL/6J (black) background. Charbon is a strictly recessive phenotype with hypopigmented fur 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).
Immune system function is largely normal in charbon mutants. Charbon mice, like allelic quicksilver and snowflake mice, display normal resistance to murine cytomegalovirus (MCMV) (MCMV Susceptibility and Resistance Screen). Charbon mutants are slightly susceptible to infection by Listeria monocytogenes, showing a 75% survival rate compared with 100% survival in wild type controls. However, they produce normal amounts of cytokines in response to Listeria infection and clear infection from the liver as well as wild type mice. In vitro, NK cells from charbon mice degranulate normally upon stimulation of Ly49H or NKp46 receptors, PMA ionomycin treatment, or upon exposure to YAC-1 cells. IFN-γ production after PMA ionomycin stimulation is also normal. The pigmentation phenotype for charbon mice is very similar to quicksilver mutants.
|Nature of Mutation|
The charbon mutation mapped to Chromosome 7, and corresponds to an A to G transition at position 1274 of the Oca2 transcript, in exon 11 of 24 total exons.
The mutated nucleotide is indicated in red lettering and results in a threonine to alanine change at amino acid 382 in the OCA2 protein.
The charbon mutation occurs in the fourth transmembrane domain of the OCA2 protein (Figure 1). It is unknown whether normal levels of the altered OCA2 protein exist in charbon mice or whether the protein is localized appropriately.
Please see the record for quicksilver for information about Oca2.
The charbon mutation results in a T382A change in the fourth transmembrane region of the OCA2 protein. This region is well-conserved between the mouse and human proteins as well as in related bacterial transporters. The change from polar threonine to nonpolar alanine may disrupt the structure of this transmembrane domain, but the effect on the structure of the protein is unknown. Threonine can undergo post-translational modifications such as phosphorylation and O-linked glycosylation, but whether this occurs at T382 in the OCA2 protein has not been tested. Human mutations in the same region cause oculocutaneous albinism.
For a further explanation of the charbon mutant phenotype, please refer to the record for quicksilver.
|Primers||Primers cannot be located by automatic search.|
Charbon 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
Char_seq(F): 5’- CAGGCAATAATTCTTCCTGGAGC-3’
Char_seq(R): 5’- GCCACTTCATTGTTCAAAAGC-3’
The following sequence of 1309 nucleotides (from Genbank genomic region NC_000073 for linear DNA sequence of Oca2) is amplified:
75601 ctggagtgag attgcctctg atatatttta taaagctaat ggtatgtttc atacagagga
75661 gtatggtgtg gagggatgga ggacctcagc aggcccaggt tgaggcatct ctcccctgag
75721 gtatcagcca tactaagggt ctagtataga atagagttag ttaggggatg ggaaggggag
75781 ttgagaaggg agtagaggca gagaaagaga gggatcagag gacagagaga gatagagaaa
75841 ggagaaagaa gaggctggct gggaacacat gagggaggag agaaagggaa agagaggaga
75901 gagagagaga gagagagaga gagagagaga gagagagaga gagagagaga gaagagtcag
75961 agtgacaaaa gggtcagaga gaggaaagag aagccaaaca gtccctttta tagacagtca
76021 ggcctatctg ctattgctaa gtaactttgg cagagcctag aaggaatgct aacacgctaa
76081 cagcctccga gtctctgagt catgcacttg ttctcatgag tatggttcac ataatgtttc
76141 atttggaaaa ttgctcttat ggcatatagt aggcacatgc atcaagaagc ccccagggta
76201 ctcagtgaac tgccctttcc gaggcaggct cggttctggc agtccctcac ttcacacttt
76261 gttctagtgg cacttggaga gtagaataga gagtgtcaat catgccaccc cactgaggaa
76321 gaccaaacca gcagtccagg caataattct tcctggagct tccaggatta gatcccctcc
76381 cttttgttca tgaatacttt ggatgtgaca gattcactgg gtcatgagtg taattcagca
76441 gtgtgataga attcaacttc aaaggcaagt ggatgcagtg tttccagctt tggcccaatg
76501 tctgcgcttg cagtaagggc agcccatttt tagagctttg ctcagtaggt tgatgcacag
76561 gattaattgg caaatttgtg ctttgattac agagacccag cctgacccac gtggtggagt
76621 ggattgattt cgagactctg gccctgctgt ttggcatggt aattacagtc ttcccagcag
76681 gatatggctc caagtctggg tccttcacta tcccacagtt gctgatccta tcattatagt
76741 caagatggca tatctcttga cagttagggc tttattgaga agtgttaata caggtctagt
76801 tattttctca gggaggaggg actggctggt gctggtttgt taactaaaga cttcatctct
76861 aaggcttttg aacaatgaag tggcatcatt atttccaaaa gttggca
PCR primer binding sites are underlined; sequencing primer binding sites are highlighted in gray; the mutated A 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||Celine Eidenschenk, Sophie Rutschmann, Bruce Beutler|
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