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|Coordinate||11,012,610 bp (GRCm38)|
|Base Change||A ⇒ C (forward strand)|
|Gene Name||solute carrier family 45, member 2|
|Synonym(s)||blanc-sale, Oca4, dominant brown, Dbr, bls, Aim1, Aim-1, Matp|
|Chromosomal Location||11,000,721-11,029,233 bp (+)|
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a transporter protein that mediates melanin synthesis. The protein is expressed in a high percentage of melanoma cell lines. Mutations in this gene are a cause of oculocutaneous albinism type 4, and polymorphisms in this gene are associated with variations in skin and hair color. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
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. [provided by MGI curators]
|Amino Acid Change||Histidine changed to Proline|
|Institutional Source||Beutler Lab|
H233P in Ensembl: ENSMUSP00000022851 (fasta)
|Gene Model||not available|
|Predicted Effect||probably damaging
PolyPhen 2 Score 0.960 (Sensitivity: 0.77; Specificity: 0.95)
|Alleles Listed at MGI|
|Mode of Inheritance||Autosomal Recessive|
|Local Stock||Sperm, gDNA|
|Last Updated||2018-08-01 4:35 PM by Diantha La Vine|
The sweater 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. Sweater mutants are viable and fertile. Sweater mutants bear a strong resemblance to galak, cardigan, and grey goose mutant animals.
|Nature of Mutation|
The sweater mutation was mapped to Chromosome 15, and corresponds to an A to C transversion at position 794 of the Slc45a2 transcript, in exon 3 of 7 total exons.
The mutated nucleotide is indicated in red lettering, and results in a histidine to proline change at amino acid 233 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 sweater mutation results in an H233P change in the sixth transmembrane domain of SLC45A2. Histidine is a polar, basic amino acid. Changing to nonpolar proline could disrupt structure, especially as proline has a rigid structure and often disrupts secondary structure motifs. This amino acid is conserved between fish, mouse and human, suggesting it may be important for SLC45A2 function (1,2). Although a proline substitution in the tenth transmembrane region occurs in uwd mice which do not have a strong phenotype (1,3), sweater mutants have a light, cream-colored coat, suggesting that the substitution of proline for histidine in the sixth transmembrane domain significantly disrupts the structure and the function of SLC45A2. A human missense mutation in the sixth transmembrane domain of human SLC45A2 causes oculocutaneous albinism that presents with little pigment, similar to sweater mice (4).
|Primers||Primers cannot be located by automatic search.|
Sweater 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. The same primers used for galak genotyping are used here.
Primers for PCR amplification
Sweater(F): 5’- CAAGCATGTAGCTAGACCTTCCACAGAGATGAAG -3’
Sweater(R): 5’- CAATGACATTGTCATCTGAAGGAACAAAGTTG -3’
1) 95°C 2:00
2) 95°C 0:30
3) 56°C 0:30
4) 72°C 2:00
5) repeat steps (2-4) 40X
6) 72°C 700
7) 4°C ∞
Primers for sequencing
Sweater_seq(F): 5’- GTGGGAAATAAACATGACTGACTGAATATG -3’
Sweater_seq(R): 5’- TTCACAAAGAACAAAGTGACTTAGCAAG -3’
The following sequence of 1277 nucleotides (from Genbank genomic region NC_000081 for linear DNA sequence of Slc45a2) is amplified:
11161 gtagctagac cttccacaga gatgaagata gatgtcaagg ttcttagatc atcccaagct
11221 agtttgtatt ttctcaagaa gcttggtggt ggaggaggat aataaaatca tctcttttta
11281 ctgccactgg aaattgattt ttatggacta atttgggtca ataatttgag ttttttgctt
11341 gttgttacgt ttttgttgtc tttaagtagt atagaggata caggttggga aggtgacagt
11401 atctccaagg acggtatttt atttgctgtg cgttcactgc tgtattgaac atttttcatt
11461 tccataccat tgaccttctt ggtaggttac ttgtatgtta ttactccata aaagatacac
11521 aggactaagg tcacagcaaa taaatgccag agatgagtct tgaacccaca ctgtcttagc
11581 ctcttgctgt gttggcgctt catcactaca ggcagtctct gctttcctca gggagctttt
11641 ccacagaagg ggaaggtctg tgcatggtgg gaaataaaca tgactgactg aatatgctaa
11701 tgcatatctc tctctgtctc tctctctctc tctcccaccc cctttgcttt ctaggttttg
11761 gaggtgccct tggctacatt ttgggtgcca tagactgggt gcatctagat ctgggaaggc
11821 tgctgggcac agaattccag gtcatgttct tcttctctgc cctggttctc atcttgtgct
11881 tcatcacaca cctgtgcagt atccctgaag ctccactcag agatgctgca actgaccctc
11941 cctcacagca ggaccctcag ggctcgtcgc tgtcagccag tgggatgcat gaatacggtt
12001 ctattgagaa agttaaaaat ggaggtgcag acacagagca gccagtacag gaatggaaaa
12061 acaaaaagcc ttctggccag gtaaagatgc aaattctttt ttctttttct ccacatgggg
12121 gaagttttct tgctaagtca ctttgttctt tgtgaaattt gtcttgtttg cttgtctgat
12181 gtgaagtttt gtgaagtcta tttgaacctt taaaacctcc cttagtcatt ccctgttgga
12241 atgagaattt tgtgcctcag tggttctctt gcctcttact cctttcaaag catcaaactg
12301 gggaaggtga gacatctgta acagtgagac catgtgagaa ctctccagcc accttctggc
12361 cacaggacat agtcttttag ataaagaatt acaatctaca actttgttcc ttcagatgac
PCR primer binding sites are underlined; sequencing primer binding sites are highlighted in gray; the mutated A 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, 981-98.
2. Fukamachi, S., Shimada, A., and Shima, A. (2001) Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka, Nat. Genet 28, 381-385.
3. Du, J. and Fisher, D. E. (2002) Identification of Aim-1 as the underwhite mouse mutant and its transcriptional regulation by MITF, J Biol. Chem. 277, 402-406.
|Science Writers||Nora G. Smart|
|Illustrators||Diantha La Vine|
|Authors||Amanda L. Blasius, Bruce Beutler|
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