Lightning bolt tail (Bolt): a new dominant mutation that affects the tail and spinal vertebrae in the mouse

Belinda Harris, Patricia Ward-Bailey, Leah Rae Donahue, Kenneth Johnson,

and Roderick T. Bronson

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

 

Mutation (allele) symbol: Bolt

Mutation (allele) name: Lightning bolt tail

Gene symbol: Bolt

Strain of origin: (BALB/cJ x A/J) F1

Current strain name: C;A-Bolt/J

Stock #: 006448 (view JAX® Mice Data Sheet for additional information including Price and Supply Information)

Phenotype categories: skeletal

 

Abstract

A new dominant skeletal mutation named lightning bolt tail (Bolt) has been found at The Jackson Laboratory. Mice carrying the Bolt mutation have kinked tails and shortened spines. This new mutation has been mapped to Chromosome 11.

Origin and Description

This novel skeletal mutation was found in 1998 in a production colony of (BALB/cJ x A/J) F1 mice at The Jackson Laboratory and was first recognized by its kinked tail. Mice carrying the Bolt mutation can be identified shortly after birth by their variable-length kinked tail (See Photo) and curved spine (See Photo). Both sexes are viable and live a normal lifespan. The Bolt colony is maintained by mating heterozygous females or males to normal wild type littermates. It is currently at the F26 generation.

Genetic Analysis

In order to determine the mode of inheritance for the Bolt mutation, a female C3H/HeSnJ mouse was mated to a Bolt/+ male. This mating produced two Bolt/+ and seven wild type progeny, proving this to be a dominant mutation. Heterozygotes mated to heterozygotes produce both normal and Bolt phenotypes. The ratio of Bolt phenotypes born is 25% which is much lower than the expected 75%, suggesting prenatal lethality of Bolt homozygotes.

Using our standard mapping protocols a linkage cross was performed by mating a heterozygous female Bolt/+ to a male CAST/Ei (Mus castaneus). This mating produced six Bolt/+ phenotypes out of seventeen progeny in the F1 generation. The heterozygote F1 Bolt/+ animals were backcrossed to the wildtype background strain. The backcross matings produced 153 progeny (49 Nm/+ and 104 +/+) of which 70 were utilized to map the Bolt mutation to Chromosome 11. This mutation maps between D11Nds7(NCBIm36 position 102.7 MB) and D11Mit128 (NCBIm36 position 113.7 MB). A search of the Mouse Genome database between these two flanking markers found no known genes with a phenotype similar to the Bolt phenotype. Two possible candidate genes in this interval are Wnt3 and Wnt9b because a hypomorphic mutation of another Wnt gene, vestigial tail (Wnt3avt) causes abnormal tail development.

Pathology

X-Rays were done on two heterozygous mutants.  They were found to have kinked tails and abnormal spinal vertebral bodies. When mice carrying the mutation are picked up by their tails, their rear legs are oriented in abnormal positions. The lumbar spine has irregularly placed vertebral bodies.

Auditory brain stem response (ABR) testing was done on three female heterozygotes and two controls. Severe hearing loss was found in all mice tested, but is likely an effect of the A/J strain background.

Eyes of two female wildtype and two male heterozygotes (Bolt/+) were examined using an opthalmascope and found to be normal for a BALB/cJ X A/J strain background.

Spinal sections are being processed for pathology. Check back in the near future for additional pathological information.

 

Discussion

We report a new dominant mutation named lightning bolt tail that is located on mouse Chromosome 11. This new mutation affects the tail and vertebral spine of affected animals. The phenotype is clearly visible on X-Rays as well as by direct observation of the mice.

Acknowledgements

The authors wish to thank HePing Yu for auditory brain stem analysis, Coleen Marden for skeletal and pathological preparations, and Leona Gagnon for technical photography.

 

 

 

 

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