A new spontaneous mutation named X-linked stripe.

Coleen Marden, Patricia F. Ward-Bailey, Leah Rae Donahue, and Kenneth R. Johnson

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: Xls

Mutation (allele) name: X-linked stripe

Gene symbol: Xls

Strain of origin:(C57BL/6J x CBA/Ca-Pdss2^kd ) F1

Current strain name: CBACaGnLe.Cg-Xls/J

Stock #:005274 (view JAX® Mice Data Sheet for additional information including Price and Supply Information)

Phenotype categories: Color

Abstract

A new spontaneous dominant X-linked mutation causing a striped coat has been characterized in the Mouse Mutant Resource (MMR) at the Jackson Laboratory and named X-linked stripe (Xls). The new mutant mice have a phenotype and chromosomal location similar to that of the previously described Tabby (Eda^Ta) mutation, but a direct test for allelism was not possible.

Origin and Description

The new X-linked stripe mutation was identified in the offspring resulting from an in vitro fertilization of C57BL/6J eggs fertilized with sperm from CBA/Ca-Pdss2^kd homozygous males in 2001. After one outcross to C3H/HeSnJ this mutation was subsequently maintained by continuous backcross of a heterozygous female to a CBA/CaGnLeJ male and reached generation N15 in 2007. Heterozygous female mice affected by the Xls mutation have an agouti coat color with stripes (See Photo)and a white patch is always observed on the left hind flank. Hemizygous mutant males do not survive past birth.

Genetic Analysis

X-linked stripe is inherited as a dominant mutation on the X Chromosome, as shown by traditional breeding, in which a heterozygous mutant female mouse was outcrossed to an unrelated C3H/HeSnJ male mouse. Mutant females were observed in the F1 mice produced by this cross proving that the mutation has dominant inheritance. A female affected with the Xls mutation was backcrossed to a CBA/CaGnLe/J male. The progeny from this cross produced normal appearing +/+ females and +/Y males and affected +/Nm females. No affected males (Nm/Y) were ever born.

Using standard MMR mapping procedures a linkage cross was set up by mating 2 female mice heterozygous for Xls with 1 male CAST/Ei mouse. Five affected F1 females from this cross were then backcrossed to +/Y males from the CBACaGnLe.Cg-Xls/J colony. These matings produced 32 affected female mice of which 21 were used for linkage analysis. Xls was confirmed to be on the X Chromosome by linkage with MIT markers DXMit113 (NCBIm 36 position 90.0 Mb) which showed no recombination with Xls, and DXMit41 (NCBIm 36 position 97.3 Mb), which showed 9.5% recombination. Although phenotype and map position are similar to those of the Tabby (Eda^Ta) mutation (NCBIm 36 position 96.1Mb), a direct test for allelism was not possible. Two other X-linked genes with similar phenotypes, striated (NCBIm 36 position 69.1Mb) and patchy fur (NCBIm 36 position 73.3Mb), were ruled out as candidate genes based on map position.

Pathology

A routine pathological screen of two mice carrying the Xls mutation at 19 weeks of age revealed no gross abnormalities.

Hearing, as assessed by auditory brainstem response (ABR) on two mutant mice and two littermate controls at 3 months of age, was normal.

The eyes of two mice carrying the Xls mutation were examined with an opthalamascope and no abnormalities were observed.

Acknowledgements

The authors wish to thank Chantal Longo-Guess and Heping Yu for hearing assessment, Norm Hawes for the eye examinations, and Rod Bronson for the pathological review.

The Jackson Laboratory