Chocolate-like 2 Jackson (chtl-2J), a possible remutation of the Rab38 gene

Richard M. Samples, Patricia F. Ward-Bailey, Leah Rae Donahue, Roderick T. Bronson, and Muriel T. Davisson

Source of Support: The research was supported by NIH/NCRR grant RR01183 to the Mouse Mutant Resources (M.T.Davisson,PI) and Cancer Center Core Grant CA34196.

Mutation (allele) symbol: chtl-2J

Mutation (allele) name: chocolate-like 2 Jackson

Gene symbol: chtl-2J

Strain of origin: B6.V-Lep^ob/J

Current strain name: B6(V)- chtl^2J/J

Stock #: 005565 (view JAX® Mice Data Sheet for additional information including Price and Supply Information) NOTE: AS of 3-6-2007 available only as cryopreserved embryos.

Phenotype categories: coat color

Abstract

A new spontaneous, recessive mutation causing a coat color dilution has been mapped to Chromosome 7, in the region where Rab38^cht is positioned. Direct tests for allelism were performed with both chocolate (cht) and chocolate-like (chtl) and the results, while indicating interaction, were inconclusive in both tests (see below). This remutation has been named chocolate-like 2 Jackson.

Origin and Description

This recessive mutation was discovered by Paula Damon in a production colony of B6.V-Lep^ob mice (stock # 0632-2) at the Jackson Laboratory on February 12, 1997. Mice homozygous for the chtl^2J mutation are recognized by a diluted coat color that appears chocolate brown. This color dilution also lightens the eyes, feet, ears, and tail of affected animals (see photo). Both sexes breed and the affected animals live a normal lifespan. An article describing a similar mutation named chocolate-like (chtl) is also available on this web site. The Lep^ob has not been seen for 25 generations and is believed to be bred out of the C57BL/6J background strain.

Genetic Analysis

Using our standard mapping protocols an intercross between B6(v)-chtl^2J/J and CAST/Ei/J F1 hybrids was set up and generated 65 affected animals for linkage analysis. The chtl^2J mutation maps to mouse Chromosome 7 distal to D7Mit230 (at 24.5cM) and proximal to D7Mit43 (at 64 cM). A previously described mutant named chocolate (cht), which has a similar phenotype to this new mutant, maps in this interval (at 46 cM) on Chromosome 7.

A direct test for allelism with mice carrying the chocolate (cht) mutation was performed by mating a female, homozygous for the new mutation, to a homozygous male from the C57BL/6J-Rab38^cht/J (stock #000976) colony. This mating produced 30 progeny in 4 litters. All of the F1s produced were not black but look close to the diluted color of the new mutation (See Photo). When F1s are mated together, two shades of the chocolate color are seen. Some progeny look like the homozygotes of the new mutation, and others like the homozygous C57BL/6J-Rab38^cht/J mice.

A second direct test for allelism with mice carrying the chocolate-like (chtl) mutation was performed by mating a female homozygote from the B6(129P2)-Nos2^tm1Lau-chtl/J strain to a male homozygote from the B6(v)-chtl^2J/J strain. From this cross, the 30 F1 animals produced had a dark grey color. When two of the grey F1s were mated together they produced 6 black and 4 dark grey progeny.

Both tests for allelism were considered inconclusive because the F2s produced in both tests resulted in two coat colors, and while indicating some interaction between the new mutation and the chocolate mutation, does not prove that the new mutation is a remutation to chocolate.

Pathology

No histopathological screen was performed.

Hearing as assessed by auditory brain stem response testing (ABR) of 8 mutants and 5 controls at 3 weeks, 3 months, 6 months and 8 months of age was determined to be normal for all, except for one 8 month old mutant that had severe hearing loss. A cross section of the ear of this same mutant mouse had fluid in the middle ear, and no cochlea or hair cell structure was seen.

Discussion

We report here a new coat color mutation that maps to Chromosome 7 in the same chromosomal position as the Rab38^{^cht}and Rab38^{^chtl}genes.

Acknowledgements

The authors wish to thank Paula Damon for the discovery of the mutant, Heping Yu for hearing assessment, and Coleen Marden for excellent technical skills.

References

MGD

URL: http://www.informatics.jax.org)

The Jackson Laboratory