Reeler 5 Jackson, a remutation of the Reln gene Belinda Harris, Patricia Ward-Bailey, Ken Johnson, Rod Bronson, Muriel D

Reeler 5 Jackson, a remutation of the Reln gene

Belinda Harris, Patricia Ward-Bailey, Ken Johnson, Rod Bronson, Muriel Davisson

Source of Support: The research was supported by NIH/NCRR grant RR01183 to the Mo

use Mutant Resources (M.T.Davisson, PI) and Cancer Center Core Grant CA34196

Mutation (allele) symbol: Reln^rl-5J

Mutation (allele) name: reeler 5 Jackson

Gene symbol: Reln

Strain of origin: C3Fe.SWV-Mbp^shi/J

Current strain name: C3Fe.SWV-Mbp^shi/J - Reln^rl-5J/J

Stock #:005562 (view JAX® Mice Data Sheet for additional information including Price and Supply Information)

Phenotype categories: neurological

Abstract

We have identified a new remutation of the reelin (Reln) gene by a direct test for allelism. The phenotype, described below, is the same as the original reeler (rl) mutation.

Origin and Description

The Reln^rl-5J remutation was discovered at The Jackson Laboratory in 2004 by Amanda Bragg in a production colony of C3Fe.SWV-Mbp^shi/J mice (Stock # 001428). Mice homozygous for this spontaneous, recessive remutation of reeler can be recognized by two weeks of age. They have difficulty with locomotion that causes a leaning side-to-side behavior as they walk. Like original reeler homozygotes, rl-5J mutants are unable to keep their hindquaters upright and frequently fall over on their sides. Females homozygous for this new remutation do breed, but male homozygotes have not. Both sexes live to adulthood. Heterozygotes for this remutation are normal.

Genetic Analysis

In order to determine the mode of inheritance, a female homozygote was mated to an unrelated C56BL/6J male. No affected offspring were observed in the F1 generation produced from this mating. Mice from this F1 generation were then mated together to produce F2s, and in this cross both affected and unaffected animals were produced, proving that the mutation is recessive.

A direct test for allelism was performed by mating two heterozygous B6C3Fe a/a-Reln^rl/J females to a heterozygous new mutant male. This mating produced two litters in which three offspring out of fifteen born were affected with the reeler phenotype, proving the new mutation to be an allele of the Reln gene.

Pathology

A routine pathological screen done on three mice homozygous for rl^5J and one control littermate showed that the neuropathology in the mutants is identical to that described for the original reeler mutation (MGD 2005); the control was normal. In mice homozygous for rl-5J, the cortex(see Fig. 1) has scrambled layering. Most noticably, the outer marginal layer, which is normally relatively cell-free, has many cells. In the hippocampus(see Fig. 2) the neurons of the hippocamal gyrus, instead of being aligned in an organized arc, are scattered in several irregular wavy layers. The cerebellum(see Fig.3) is small with scrambled Purkinjie and granule cells.

Hearing tests as assessed by auditory brain stem response (ABR) on individual animals showed normal thresholds and wave pattern.

Eye examination showed all animals had retinal degeneration-1; which is a characteristic of the C3Fe.SWV-Mbp^shi/J strain and not caused by the rl-5J mutation.

Acknowledgements

The authors would like to thank Amanda Bragg for discovery of the mutant mice, Norm Hawes for examination of the eyes, Heping Yu for hearing assessement, and Coleen Marden for excellent technical expertise.

References

Mouse Genome Database (MGD) Mouse Genome Informatics Project, The Jackson Laboratory, Bar Harbor, Maine. World Wide Web

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

The Jackson Laboratory