Reeler 8 Jackson: a remutation in the Reln gene.

Authors: Son Yong Karst, Patricia F. Ward-Bailey, Richard Samples, Kenneth R. Johnson, Leah Rae Donahue, and Muriel T. Davisson

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.

Mutation (allele) symbol: rl-8J

Mutation (allele) name: reeler 8 Jackson

Gene symbol: Reln

Strain of origin: C57BL/6J

Current strain name: STOCK-Reln^rl-8J/J

Stock #: 8764 (view JAX® Mice Data Sheet for additional information including Price and Supply Information)

Phenotype categories: neurological

Origin and Description

The new reeler 8 Jackson mutation was induced by ENU mutagenesis of C57BL/6J mice at The Jackson Laboratory and was discovered by Simon John. This mutation reflects four genetic backgrounds that were known to be C57BL/6J, C3Heb/FeJ, C3H/HeH and 101/H.

Mice homozygous for the reeler 8 Jackson mutation are recognized at two weeks of age by their unsteady gait. Mutants are unable to keep their hindquarters upright and frequently fall over on their sides when walking or running. Homozygous mice die at around 3 weeks of age. The rl-8J colony is maintained by breeding hosts of homozygous ovarian transplanted mice to +/? sibling male mice and then intercrossing the heterozygous offspring.

Genetic Analysis

In order to determine the mode of inheritance of this mutation, the ovaries of a reeler 8 Jackson homozygote were transplanted into a carrier mouse and this transplanted mouse was then mated to a CAST/EiJ mouse. The F1 hybrid mice produced from this mating showed a normal looking phenotype, proving that this mutation has recessive inheritance.

Based on phenotypic similarities to the previously described Reln^rl mutation, a direct test for allelism was performed by mating mice heterozygous for this new mutation to a heterozygous C57BL/6J-Reln^rl-7J mouse. This mating produced 20 progeny, of which 6 pups had the Reln^rl-7J mutant phenotype proving allelism.

The original Reln^rl allele comprises, minimally, a 150 kd deletion between D5Mit61 and D5Mit72 [MGI Ref ID J:24458]. Sequencing data has not been generated for the rl-8J mutation.

Pathology

A routine pathological examination of one homozygous mouse at 3.5 weeks of age showed neuropathology identical to the original reeler mutation (MGD 2008). The rl-8J mutation expressed scrambled layering in the cortex. Neurons of the hippocampal gyrus are scattered in irregular wavy layers, and the cerebellum is small with scrambled Purkinje and granule cells.

The eyes of two homozygous mutant mice at 2 months of age were tested by electroretinogram (ERG) and were determined to be normal and histology performed on the same 2 mice showed no significant abnormalities. One heterozygote tested by ERG was normal.

Hearing, as assessed by auditory brainstem response testing (ABR), on two mutant mice at 3 weeks of age showed normal hearing.

Acknowledgements

We thank Simon John for discovery of the mutant, Roderick Bronson and Coleen Kane for pathological screening, Chantal Longo-Guess for hearing assessment, Norm Hawes and Ron Hurd for eye examinations.

The Jackson Laboratory