Phenotypic Mutation 'grey_goose' (pdf version)
Allelegrey_goose
Mutation Type missense
Chromosome15
Coordinate11,003,067 bp (GRCm39)
Base Change T ⇒ C (forward strand)
Gene Slc45a2
Gene Name solute carrier family 45, member 2
Synonym(s) Aim1, Dbr, blanc-sale, dominant brown, Aim-1, Matp, bls, Oca4
Chromosomal Location 11,000,807-11,029,319 bp (+) (GRCm39)
MGI Phenotype 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]
Accession Number

NCBI RefSeq: NM_053077; MGI: 2153040

MappedYes 
Amino Acid Change Leucine changed to Proline
Institutional SourceBeutler Lab
Gene Model not available
AlphaFold P58355
SMART Domains Protein: ENSMUSP00000112408
Gene: ENSMUSG00000022243
AA Change: L180P

DomainStartEndE-ValueType
Pfam:MFS_2 1 457 2e-22 PFAM
Pfam:MFS_1 2 292 2.6e-12 PFAM
Predicted Effect probably damaging

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
(Using ENSMUST00000117100)
Meta Mutation Damage Score Not available question?
Is this an essential gene? Probably nonessential (E-score: 0.094) question?
Phenotypic Category Autosomal Recessive
Candidate Explorer Status loading ...
Single pedigree
Linkage Analysis Data
Penetrance 100% 
Alleles Listed at MGI

All alleles(11) : Targeted, other(1) Spontaneous(5) Chemically induced(5)

Lab Alleles
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02074:Slc45a2 APN 15 11000903 start codon destroyed probably null 0.80
IGL02283:Slc45a2 APN 15 11001268 missense probably damaging 1.00
IGL02634:Slc45a2 APN 15 11023440 missense probably benign 0.21
IGL03039:Slc45a2 APN 15 11012773 missense probably benign
IGL03123:Slc45a2 APN 15 11012741 missense probably benign 0.01
IGL03226:Slc45a2 APN 15 11022278 missense probably damaging 1.00
cardigan UTSW 15 11022257 synonymous probably benign
cheng UTSW 15 11025954 missense probably damaging 0.99
Draco2 UTSW 15 11000903 start codon destroyed probably benign 0.05
galak UTSW 15 11012752 missense probably benign
goku UTSW 15 11000941 nonsense probably null
june_gloom UTSW 15 11023529 missense possibly damaging 0.94
nilla UTSW 15 splice donor site
Olaf UTSW 15 unclassified
sweater UTSW 15 11012696 missense probably damaging 1.00
voldemort UTSW 15 unclassified
yuki UTSW 15 11001178 missense probably damaging 1.00
zuckerkuss UTSW 15 11026020 critical splice donor site probably benign
R0148:Slc45a2 UTSW 15 11025954 missense probably damaging 0.99
R0433:Slc45a2 UTSW 15 11025831 missense probably benign 0.17
R0440:Slc45a2 UTSW 15 11000903 start codon destroyed probably benign 0.05
R0675:Slc45a2 UTSW 15 11025864 missense probably damaging 1.00
R1384:Slc45a2 UTSW 15 11025832 missense probably benign 0.04
R1616:Slc45a2 UTSW 15 11022214 missense probably null 0.01
R1824:Slc45a2 UTSW 15 11022172 missense probably damaging 0.99
R2244:Slc45a2 UTSW 15 11003087 missense probably benign 0.21
R3761:Slc45a2 UTSW 15 11012800 missense probably benign 0.07
R4631:Slc45a2 UTSW 15 11012662 missense probably benign 0.13
R4756:Slc45a2 UTSW 15 11028016 nonsense probably null
R4990:Slc45a2 UTSW 15 11001236 missense probably benign 0.00
R5066:Slc45a2 UTSW 15 11012693 missense probably benign 0.31
R5209:Slc45a2 UTSW 15 11027871 missense probably damaging 0.98
R5210:Slc45a2 UTSW 15 11027871 missense probably damaging 0.98
R5211:Slc45a2 UTSW 15 11027871 missense probably damaging 0.98
R5212:Slc45a2 UTSW 15 11027871 missense probably damaging 0.98
R5213:Slc45a2 UTSW 15 11027871 missense probably damaging 0.98
R5259:Slc45a2 UTSW 15 11027871 missense probably damaging 0.98
R5261:Slc45a2 UTSW 15 11027871 missense probably damaging 0.98
R5390:Slc45a2 UTSW 15 11027871 missense probably damaging 0.98
R5394:Slc45a2 UTSW 15 11027871 missense probably damaging 0.98
R5395:Slc45a2 UTSW 15 11027871 missense probably damaging 0.98
R5422:Slc45a2 UTSW 15 11027871 missense probably damaging 0.98
R5496:Slc45a2 UTSW 15 11027871 missense probably damaging 0.98
R5498:Slc45a2 UTSW 15 11027871 missense probably damaging 0.98
R5499:Slc45a2 UTSW 15 11027871 missense probably damaging 0.98
R5500:Slc45a2 UTSW 15 11027871 missense probably damaging 0.98
R5501:Slc45a2 UTSW 15 11027871 missense probably damaging 0.98
R5649:Slc45a2 UTSW 15 11012693 missense probably benign 0.00
R5662:Slc45a2 UTSW 15 11022169 missense probably benign 0.31
R5696:Slc45a2 UTSW 15 11001219 missense probably damaging 1.00
R5896:Slc45a2 UTSW 15 11000941 nonsense probably null
R6236:Slc45a2 UTSW 15 11022158 missense probably benign 0.00
R6709:Slc45a2 UTSW 15 11001216 missense possibly damaging 0.46
R7243:Slc45a2 UTSW 15 11023436 missense possibly damaging 0.94
R7839:Slc45a2 UTSW 15 11027835 missense probably benign
R8221:Slc45a2 UTSW 15 11001233 missense probably benign 0.02
R8404:Slc45a2 UTSW 15 11027958 missense possibly damaging 0.62
R8502:Slc45a2 UTSW 15 11027958 missense possibly damaging 0.62
R8680:Slc45a2 UTSW 15 11000972 missense probably benign 0.00
R8724:Slc45a2 UTSW 15 11012610 missense probably benign 0.00
R8966:Slc45a2 UTSW 15 11001122 missense probably damaging 1.00
R9431:Slc45a2 UTSW 15 11026005 missense possibly damaging 0.94
Mode of Inheritance Autosomal Recessive
Local Stock Embryos, gDNA
Repository

none

Last Updated 2018-08-01 4:33 PM by Diantha La Vine
Record Created unknown
Record Posted 2008-04-15
Phenotypic Description

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.

619 GACAAGGAGAAGGGCCTCCACTACCATGCCCTC
175 -D--K--E--K--G--L--H--Y--H--A--L-
 
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.
Illustration of Mutations in
Gene & Protein
Protein Prediction
Figure 1. Protein topology and domain structure of SLC45A2. SLC45A2 is a 55kD protein with 12 membrane-spanning (TM) domains, an elongated N-terminus, and enlarged cytoplasmic loop between transmembrane domains six and seven. The sucrose-transporter signature sequence, R-W-G-R-R is noted. The grey goose mutation (red asterisk) results in a leucine to proline change at amino acid 180 of the SLC45A2 protein.  This image is interactive. Click on the mutations for more specific information. 
The grey goose mutation occurs in the cytosolic loop between the fourth and fifth transmembrane domains of the SLC45A2 protein (Figure 1). It is unknown whether normal levels of the altered protein protein exist in grey goose mice or whether this protein is localized appropriately.
 
Please see the record for cardigan for more information on Slc45a2.
Putative Mechanism
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.
Primers Primers cannot be located by automatic search.
Genotyping
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’
 
PCR program
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
2581 attcgtct   
                                                         
 
PCR primer binding sites are underlined; sequencing primer binding sites are highlighted in gray; the mutated T is shown in red text.
References
Science Writers Nora G. Smart
Illustrators Diantha La Vine
AuthorsCeline Eidenschenk, Amanda L. Blasius, Bruce Beutler
Edit History
2011-08-25 11:56 AM (current)
2011-01-07 9:08 AM
2010-07-07 2:52 PM
2010-07-07 2:51 PM
2010-07-07 2:51 PM
2010-02-03 9:35 AM