Phenotypic Mutation 'killer_whale' (pdf version)
Allelekiller_whale
Mutation Type
Chromosome2
Coordinate
Base Change
Gene a
Gene Name nonagouti
Synonym(s) ASP, As, agouti, agouti signal protein
Chromosomal Location 154,791,402-155,051,012 bp (+)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] In mice, the agouti gene encodes a paracrine signaling molecule that causes hair follicle melanocytes to synthesize pheomelanin, a yellow pigment, instead of the black or brown pigment, eumelanin. Pleiotropic effects of constitutive expression of the mouse gene include adult-onset obesity, increased tumor susceptibility, and premature infertility. This gene is highly similar to the mouse gene and encodes a secreted protein that may (1) affect the quality of hair pigmentation, (2) act as a pharmacological antagonist of alpha-melanocyte-stimulating hormone, (3) play a role in neuroendocrine aspects of melanocortin action, and (4) have a functional role in regulating lipid metabolism in adipocytes. [provided by RefSeq, Jul 2008]
PHENOTYPE: Agouti acts in the hair follicles, primarily affecting the relative amount and distribution of yellow pigment (phaeomelanin) and black pigment (eumelanin) in hairs of the coat. Some alleles show lethal effects or are associated with obesity. [provided by MGI curators]
Accession Number

NCBI RefSeq: NM_015770; MGI:87853

MappedNo 
Amino Acid Change
Institutional SourceBeutler Lab
Ref Sequences
Ensembl: ENSMUSP00000105319 (fasta)
Gene Model not available
AlphaFold Q03288
SMART Domains

DomainStartEndE-ValueType
Agouti 6 127 3.98e-69 SMART
Meta Mutation Damage Score Not available question?
Is this an essential gene? Probably nonessential (E-score: 0.178) question?
Phenotypic Category
Phenotype question? Literature verified References
pigmentation
skin/coat/nails
Candidate Explorer Status CE: no linkage results
Single pedigree
Linkage Analysis Data
Penetrance  
Alleles Listed at MGI

All alleles(401) : Targeted(1) Gene trapped(296) Spontaneous(58) Chemically induced(16) Radiation induced(30) Other(1)

Lab Alleles
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00839:a APN 2 155045673 missense probably benign 0.00
IGL02421:a APN 2 155050752 missense probably damaging 0.98
garfield UTSW 2 unclassified
split UTSW 2 unclassified
yellowbelly UTSW 2 unclassified
R0670:a UTSW 2 155045758 missense probably damaging 1.00
R2114:a UTSW 2 155047729 missense probably benign
R4082:a UTSW 2 155045758 missense probably damaging 1.00
R4346:a UTSW 2 155045731 missense probably benign 0.20
R6188:a UTSW 2 155047682 missense probably damaging 0.99
R6476:a UTSW 2 155050779 missense probably benign 0.00
R7211:a UTSW 2 155045779 missense probably damaging 1.00
R7295:a UTSW 2 155045758 missense probably damaging 1.00
R8776:a UTSW 2 155050692 missense probably damaging 0.99
R8776-TAIL:a UTSW 2 155050692 missense probably damaging 0.99
Mode of Inheritance Unknown
Local Stock Sperm, gDNA
Repository

None

Last Updated 2021-10-06 11:54 AM by Diantha La Vine
Record Created unknown
Record Posted 2014-05-22
Phenotypic Description

The killer whale mouse arose as a spontaneous mutant in the aoba stock (Figure 1). The mouse's dorsal coat is solid black, but the ventral coat is tan, similar to the black and tan (at; MGI:1855941) mouse carrying a mutation in the agouti locus.

Nature of Mutation

The coat color phenotype of killer whale mice strongly suggested a mutation of agouti; this has not been verified by complementation testing and the nature of the mutation is not known.

Illustration of Mutations in
Gene & Protein
Protein Prediction
Figure 2. The domain structure of agouti signaling protein (ASP). ASP has a cleavable signal peptide (SIG; amino acids 1-22), a hydrophobic region (HYD; amino acids 40-50), a lysine/arginine-rich basic domain (BASIC; amino acids 57-85), and a cysteine-rich C-terminus (CYS; amino acids 92-131). Asparagine 39 is predicted to be N-linked glycosylated. Regions 1, 2 and 3 are described on the yellowbelly page.

The agouti (a; alternatively, nonagouti) gene encodes the 131-amino acid secreted agouti signaling protein (ASP) (Figure 2). ASP functions in pigment type switching in melanocytes by inhibiting the function of the melanocortin 1 receptor (MC1R), subsequently promoting the production of pheomelanin (red/yellow pigment).

 

For more information about a, please see the record yellowbelly.

Putative Mechanism

The phenotype observed in the killer whale mice resembles that of the at (black and tan; MGI:1855941) mice in that the at mice exhibit black coloration dorsally and have a yellow ventrum (1). TThe a mutation in the at mice is a spontaneous 6 kb insertion between exon 1C and exon 2 (~2.1 kb 3’ from exon 1C); the insertion contains a retrovirus-like transposable element VL30 with an internal 526 bp direct repeat (2). IAs a result of the VL30 insertion, the hair cycle-specific promoter/regulatory elements that control a expression on the dorsum are impaired. In the at mice, most, if not all, expression of a is believed to be controlled by the ventral-specific promoter. In the at mice, yellow pigment is synthesized throughout the hair cycle, leading to a ventrum that is yellow, while the dorsal hairs are black (3). We hypothesize that the expression pattern of a in killer whale mice mimics that in the at mice.

Primers Primers cannot be located by automatic search.
References
Science Writers Anne Murray
Illustrators Peter Jurek
AuthorsCarrie N. Arnold, Bruce Beutler