|Coordinate||11,002,981 bp (GRCm38)|
|Base Change||T ⇒ C (forward strand)|
|Gene Name||solute carrier family 45, member 2|
|Synonym(s)||Aim-1, Aim1, Dbr, Matp, blanc-sale, bls, uw|
|Chromosomal Location||11,000,721-11,029,233 bp (+)|
|MGI Phenotype||Homozygotes for spontaneous mutations exhibit varied degrees of hypopigmentation of the eyes, skin, and hair, especially the underfur. Eyes are very light at birth but darken with age.|
|Amino Acid Change||Leucine changed to Proline|
|Institutional Source||Beutler Lab|
L180P in Ensembl: ENSMUSP00000022851 (fasta)
|Gene Model||not available|
|Predicted Effect||probably damaging
PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|Phenotypic Category||pigmentation, skin/coat/nails|
|Alleles Listed at MGI|
|Mode of Inheritance||Autosomal Recessive|
|Local Stock||Embryos, gDNA|
|Last Updated||10/30/2014 1:59 PM by Stephen Lyon|
The grey goose mutation was induced by ENU mutagenesis on the C57BL/6J (black) background, and was discovered in G3 animals. Homozygous mutant mice exhibit a "dirty white" coat color associated with a light ocular albinism. Newborn mutants have very light-colored skin and eyes in comparison with their heterozygote littermates. Their eyes darken during development until only a light red glint remains in adults. Grey goose mutants are viable and fertile. Grey goose mutants bear a strong resemblance to galak, sweater, and cardigan mutant animals.
|Nature of Mutation|
The grey goose mutation was mapped to Chromosome 15, and corresponds to a T to C transition at position 635 of the Slc45a2 transcript, in exon 2 of 7 total exons.
The mutated nucleotide is indicated in red lettering, and results in a leucine to proline change at amino acid 180 of the SLC45A2 (solute carrier family 45, member 2) or MATP (membrane associated transporter protein) protein.
Please see the record for cardigan for more information on Slc45a2.
The grey goose mutation results in an L180P change near the fifth transmembrane domain of SLC45A2. This region is well-conserved in fish, mice and humans (1,2). Although both leucine and proline are nonpolar hydrophobic residues, proline has a rigid conformation that often disrupts secondary structure, and is often found in turns and loops. Although L180 is not located within the fifth transmembrane domain, the substitution of proline near the transmembrane domain may disrupt the structure of the protein in this region. A human mutation in this region causes oculocutaneous albinism with patients presenting with very little pigment, suggesting this region of the SLC45A2 protein is functionally important.
Grey goose 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. This protocol has not been tested.
Primers for PCR amplification
Goose(F): 5’- ACCAAAACAAGGTGATTTGATGGGAGTT -3’
Goose(R): 5’- AGACGAATGCCCCGAGGCT - 3’
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
Goose_seq(F): 5’- AAGGTGATTTGATGGGAGTTTAAGTG -3’
Goose_seq(R): 5’- GCAGTGTTCTGAAGAAACCTC -3’
The following sequence of 578 nucleotides (from Genbank genomic region NC_000081 for linear DNA sequence of Slc45a2) is amplified:
2011 accaaaacaa ggtgatttga tgggagttta
2041 agtgaaataa aaaatatgtg ggttgtttaa acctgattta gaaggcctat gtttgttttt
2101 cttttagctt tggttgctaa cccaaggcag aagctgatct gggccataag catcaccatg
2161 gtaggtgtgg ttctcttcga tttttctgct gacttcattg acgggcccat caaagcctac
2221 ttatttgatg tctgctccca ccaggacaag gagaagggcc tccactacca tgccctcttc
2281 acaggtaggg aatattccag aaagctggtc catccgcttt gcagacaggg agaaatgtca
2341 gcggacgcat ccagtgtctc tgcacttaga accttttgga tgaatgggtc agttgatagg
2401 aagtgcctat cacgcgctct ggcccgtctc catctgtgtc cctgaacaaa gtaagctcat
2461 gactgggctg cagagttcct gaaaaggaag tttacataag aggtttcttc agaacactgc
2521 aaaatgtagg aaggagtcct gtgcactgaa cattctcttt aaagcaatga gcctcggggc
PCR primer binding sites are underlined; sequencing primer binding sites are highlighted in gray; the mutated T is shown in red text.
1. Newton, J. M., Cohen-Barak, O., Hagiwara, N., Gardner, J. M., Davisson, M. T., King, R. A., and Brilliant, M. H. (2001) Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4, Am. J Hum. Genet 69, 981-988.
|Science Writers||Nora G. Smart|
|Illustrators||Diantha La Vine|
|Authors||Celine Eidenschenk, Amanda L. Blasius, Bruce Beutler|