Phenotypic Mutation 'zuckerkuss' (pdf version)
Allelezuckerkuss
Mutation Type critical splice donor site (1 bp from exon)
Chromosome15
Coordinate11,026,020 bp (GRCm39)
Base Change G ⇒ T (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
Institutional SourceBeutler Lab
Gene Model not available
AlphaFold P58355
SMART Domains Protein: ENSMUSP00000112408
Gene: ENSMUSG00000022243

DomainStartEndE-ValueType
Pfam:MFS_2 1 457 2e-22 PFAM
Pfam:MFS_1 2 292 2.6e-12 PFAM
Predicted Effect probably benign
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
grey_goose UTSW 15 11003067 missense probably damaging 1.00
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
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 Sperm, gDNA
Repository

none

Last Updated 2018-08-01 4:39 PM by Diantha La Vine
Record Created 2010-01-18 12:00 AM
Record Posted 2010-01-26
Phenotypic Description

The zuckerkuss mutation was induced by ENU mutagenesis on the C57BL/6J (black) background and was discovered in G3 animals. The mutant mice exhibit a “dirty white” coat color and red eyes (Figure 1).  

Nature of Mutation
The Slc45a2 gene was directly sequenced and a mutation corresponding to a G to T transversion in the donor splice site of intron 6 was found (position 25214 in Genbank genomic region NC_000081 for linear genomic DNA sequence of Slc45a2). Slc45a2 contains 7 exons encoding 530 translated amino acids. The effect of the mutation at the cDNA and protein level has not been determined. One possibility, shown below, is that aberrant splicing results in skipping of exon 6, and a frameshift that creates a premature stop codon at the beginning of exon 7 with truncation occurring after amino acid 385.
 

       <--exon 5      <--exon 6 intron 6-->      exon 7-->
22736 GTTTATTCAT......GAGAAAGAG GTGGGTGACAA......AAGGGGCAG 27003
383   -V--Y--S--......-E--K--E-                  *         385
       correct         deleted                   aberrant

 
The donor splice site of intron 6, which is destroyed by the zuckerkuss mutation, is indicated in blue; the mutated nucleotide is indicated in red.
Illustration of Mutations in
Gene & Protein
Protein Prediction
Figure 2. 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 zuckerkuss mutation causes premature truncation that occurs near the end of the eighth transmembrane domain of the SLC45A2 protein. This image is interactive. Click on the mutations for more specific information. 
The zuckerkuss mutation causes premature truncation that occurs near the end of the eighth transmembrane domain of the SLC45A2 protein. It is unknown whether normal levels of the altered protein exist in zuckerkuss mice or whether this protein is localized appropriately.
 
Please see the record for cardigan for more information about Slc45a2.
Putative Mechanism

The premature truncation of SLC45A2 caused by the zuckerkuss mutation is likely to result in a protein that is unable to localize appropriately to the membrane. Zuckerkuss mice have a severe hypopigmentation phenotype that resembles other alleles of Slc45a2 resulting in nonfunctional protein. These include alleles that cause premature truncation of SLC45A2 such as cardigan and underwhite (1-3). Similarly, humans with SLC45A2 mutations causing protein truncation in the seventh or ninth transmembrane domains have very little pigmentation in their skin and eyes (4).

Primers Primers cannot be located by automatic search.
Genotyping
Zuckerkuss genotyping is performed by amplifying the region containing the mutation using PCR, followed by sequencing of the amplified region to detect the single nucleotide transition. 
 
Primers
Zucker(F): 5’- AGAGTCAGCAAGGCAACTTCATGC -3’
Zucker(R): 5’- GGTAAGGGTTAAGTCACCGTTCCAG -3’
 
PCR program
1) 95°C             2:00
2) 95°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
Zucker_seq(F): 5'- TGCAAAGGATTTAAAACTGATCCCC -3'
Zucker_seq(R): 5’- CCTTAGATCAGGGGTAGCATCAC -3’
 
The following sequence of 838 nucleotides (NCBI Mouse Genome Build 37.1, Chromosome 15, bases 10,955,248 to 10,956,085; Genbank genomic region: NC_000081) is amplified:
 
  1 agagtcagca aggcaacttc atgctgtctt ttatgcaaag gatttaaaac tgatccccaa
 61 agccagctgt ttctggcaca cagataagga agtattttgt ttctgactca gtatcaaagg
121 aagtcgtcta aaaaggaaag tgcatcttca aaagaaagga ttatctgaag ttattagata
181 ttgtgcggca ctgccagctg taattttccc ccctttattc tctctacaga ctttcagaaa
241 gctatggtct cctacattgg attaaaaggc ctttatttca tgggatattt gctctttggc
301 ctgggaacag gattcatagg actctttcca aatgtgtact ctactctggt cctctgttct
361 atgtttggtg taatgtccag cacattgtac actgtgccct ttaacctcat tgctgagtac
421 caccgtgaag aggagaaaga ggtgggtgac aaagggaatt tacctcaagg ataagggaag
481 gaaggaagga aggaaggaag gcagaaggat gcttaaacaa gtataaccat gcaaacatga
541 ctacaaagct aggagagttc tctctttgct gtgaatccct atgcaccttt tgaattttag
601 gacaatgata gtgaccccaa atatctgatt aaagtaggta ggctcactga tgatgagaaa
661 tgagtccttg atcagactga gacaaagagg ccctatgtct tttgcaacca ctctaaggag
721 ctttcaacat cgcagcattt ctagatgccc acagtgatgc tacccctgat ctaaggtaca
781 gagaagcatg gtggcatttc ttgcggttac agtctggaac ggtgacttaa cccttacc
 
Primer binding sites are underlined; sequencing primer binding sites are highlighted in gray; the mutated G is indicated in red.
References
Science Writers Nora G. Smart
Illustrators Nora G. Smart, Diantha La Vine
AuthorsChristina Neppl, Bruce Beutler
Edit History
2011-08-25 12:05 PM (current)
2011-01-07 9:09 AM
2010-07-07 2:47 PM
2010-07-07 2:47 PM
2010-02-25 2:51 PM