Phenotypic Mutation 'killer_whale'

• Allele: killer_whale
• Chromosome: 2
• Gene: a
• Gene Name: nonagouti
• Synonym(s): agouti, As, ASP, agouti signal protein
• Chromosomal Location: 154,792,519-154,892,932 bp (+) (GRCm39)
• 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]
• Mapped: No
• Institutional Source: Beutler Lab
• Ref Sequences:
  Ensembl: ENSMUSP00000105319
• Gene Model: not available
• AlphaFold: Q03288
• Meta Mutation Damage Score: Not available
• Is this an essential gene?: Probably nonessential (E-score: 0.220)
• Phenotypic Category: Unknown
• Mode of Inheritance: Unknown
• Local Stock: Sperm, gDNA
• Last Updated: 2021-10-06 11:54 AM by Diantha La Vine
• Record Created: unknown
• Record Posted: 2014-05-22
• Science Writers: Anne Murray
• Illustrators: Peter Jurek
• Authors: Carrie N. Arnold, Bruce Beutler

Accession Number

NCBI RefSeq: NM_015770; MGI:87853

Alleles Listed at MGI

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

Repository

None

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 (a^t; 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.

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 a^t (black and tan; MGI:1855941) mice in that the a^t mice exhibit black coloration dorsally and have a yellow ventrum (1). TThe a mutation in the a^t 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 a^t mice, most, if not all, expression of a is believed to be controlled by the ventral-specific promoter. In the a^t 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 a^t mice.

Primers

Primers cannot be located by automatic search.

References

  1. Dunn, L. C. (1928) A Fifth Allelomorph in the Agouti Series of the House Mouse. Proc Natl Acad Sci U S A. 14, 816-819.

  2. Bultman, S. J., Klebig, M. L., Michaud, E. J., Sweet, H. O., Davisson, M. T., and Woychik, R. P. (1994) Molecular Analysis of Reverse Mutations from Nonagouti (a) to Black-and-Tan (a(t)) and White-Bellied Agouti (Aw) Reveals Alternative Forms of Agouti Transcripts. Genes Dev. 8, 481-490.

  3. Vrieling, H., Duhl, D. M., Millar, S. E., Miller, K. A., and Barsh, G. S. (1994) Differences in Dorsal and Ventral Pigmentation Result from Regional Expression of the Mouse Agouti Gene. Proc Natl Acad Sci U S A. 91, 5667-5671.