Reeler 4 Jackson (Relnrl-4J), a remutation of the Reln gene
Coleen C. Marden, Patricia F. Ward Bailey, Roderick T Bronson, and Kenneth R. Johnson
Source of Support:This research was supported by NIH/NCRR grant RR01183 to the Mouse Mutant Resource (M.T. Davisson, PI) and Cancer Center Core Grant CA34196
Gene symbol:Reln
Mutation (allele) symbol: rl-4J
Mutation (allele) name: reeler 4 Jackson
Strain of origin: B6.129-IrflMtm1Mak
Current strain name: B6.129-IrflMtm1Mak Relnrl-4J/J
Stock #:005250 (view JAX® Mice Data Sheet for additional information including Price and Supply Information)
Phenotype categories: size, neurological
Abstract
We have identified the fourth allele of the reelin (Reln) gene by a direct test for allelism. Both the phenotype and pathology described below, are the same as the original reeler (rl) mutation with the exception that this new remutation has earlier lethality.
Origin and Description
The Relnrl-4J remutation was discovered at the Jackson Laboratory in 2003 by Tina Morse in a production colony of B6.129-IrflMtm1Mak mice. Mice homozygous for the Relnrl-4Jremutation can be recognized by two weeks of age. They have difficulty with locomotion that causes a leaning side-to-side behavior as they walk and are smaller than their unaffected littermates. Like the original reeler homozygotes, rl-4J mutants are unable to keep there hindquaters upright and frequently fall over on their sides. Some mice homzygous for the Relnrl-4J remutation die by weaning age but others housed with their parents have lived longer. Both male and female heterozygotes breed and live a normal life span.
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 a female homozygote B6C3Fe-a/a-Relnrl/J mouse to a male heterozygous for this new remutation. This mating produced 21 offspring in 6 litters, of which 7 progeny were affected with the Relnrl phenotype, proving the new mutation to be an allele of the Reln gene.
Pathology
A routine pathological screen of two mice homozygous for the Relnrl-4J mutation at 3weeks and 3.5 weeks of age and a control at 3.5 weeks of age showed that the neuropathology of the brain is identical to that described for the original reeler mutation (MGD 2008); the control was normal. The mutants displayed the "scrambled" cerebellum and cortex seen in the original reeler mutation and all other reeler alleles. The Relnrl-4J mutants showed scrambled layering in the cortex, neurons of the hippocampal gyrus are scattered in irregular wavy layer and the cerebellum is smaller with scrambled Purkinjie and granule cells.
Discussion
The Relnrl-4J mutation ,like the Relnrl-7J has earlier lethality than the original Relnrl which may be due to a strain background effect. The original Relnrl is maintained on a hybrid background (rl/rl X B6C3F1).
Acknowledgements
The authors thank Tina Morse for mutant discovery, and Norm Hawes and Rod Hurd for the eye examinations.
