Variable spot and size: A new dominant spotting mutation on mouse Chromosome 2

Belinda Harris, Pat Ward-Bailey, Ken Johnson and Rod Bronson

Source of Support: The research was supported by NIH/NCRR grant RR001183 to the Mouse Mutant Resource (M. T. Davisson, PI) and Cancer Center Core Grant CA34196.

Mutation (allele) symbol: Vss

Mutation (allele) name: variable spot and size

Gene symbol: Vss

Strain of origin: B6EiC3Sn-a/A-Gy/J

Current strain name: B6EiC3-a/A-Vss/GrsrJ

Stock #:006450 (View JAX®Mice Data Sheet for additional information including Price and Supply Information) 

Phenotype categories: color, size

 

Abstract

A new dominant spotting mutation named Variable Spot and Size (Vss) has been found at The Jackson Laboratory. In comparison to their normal littermates, mice heterozygous for the Vss mutation are recognized by a small, variably sized belly spot and an overall smaller body size. A linkage cross to CAST/Ei was utilized to map this mutation to Chromosome 2.

Origin and Description

This mutation was discovered by Jane Farley in a colony of  B6EiC3Sn-a/A-Gy/J mice at The Jackson Laboratory. Mice carrying the Vss mutation are recognized as having a white belly spot (See Photo) and an overall smaller body size (See Photo). Both male and female heterozygotes are viable, live a normal lifespan, and breed well.  This colony is maintained by mating heterozygous Vss mice to the B6EiC3H-a/A F1 background strain.

Genetic Analysis

Using our standard mapping protocols, a CAST/Ei mouse was mated to a heterozygote Vss mouse and produced 13 mutants out of 32 progeny in the F1 generation. Some progeny produced from this mating displayed the Vss phenotype proving dominant inheritance.The CAST/ Vss F1s were backcrossed to wildtype B6EiC3H-a/A F1 mice and produced 285 progeny that were used to map Vss to Chromosome 2. The Vss mutation was mapped between D2Mit300 (NCBIm36 position 100.9 Mb) and D2Mit58 (NCBIm36 position 108.0 Mb).

Pathology

Eight heterozygous Vss mice and littermate controls were sent to pathology for a routine pathological screen. Four of the Vss mice 2-3.5 months of age were found to have no gross abnormalities. Four Vss mice aged 16-18 months showed lesions such as degeneration of the liver and abnormal cells in the pancreas, which are common in older animals and probably not the result of the Vss mutation.

ABR testing was done on four heterozygotes and five controls;all mice tested were found to have normal hearing.

Eyes of two Vss heterozygote mutants and controls at four and seven months of age were examined with an ophthalmoscope and found to be normal.

Discussion

We report a new spotting mutation named variable spot and size (Vss), which appears as a small to large sized white belly spot on the affected mice, as well as having a smaller body size than littermates. It has been mapped to Chromosome 2. A search in Mouse Genome Informatics (MGI) for other mutations causing color spotting and small body size yielded Pax6 (NCBIm36 position 105.4 Mb), which may be a candidate gene for Vss. The Pax6 mutants however also show a wide range of eye, craniofacial, and forebrain phenotypes that are not observed in the Vss mutant mice. A previously described mutant, lethal spotting (Edn3ls) with a similar phenotype also maps to Chromosome 2, but is more distal at (NCBIm36 position 174.4 Mb) and was ruled out as a candidate gene.

Acknowledgements

The authors wish to thank Heping Yu for auditory brain stem analysis, Coleen Marden for pathological preparations and Norm Hawes for eye examinations of these mice.

 

 

Last Modified: September 09, 2013