Purkinje Cell Degeneration 7 Jackson, a remutation of the Agtpbp1 gene.
Richard M. Samples, Patricia F. Ward-Bailey, Leah Rae Donahue, Roderick T. Bronson, and Muriel T. Davisson
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: Agtpbp1pcd-7J/J
Mutation (allele) name: Purkinje Cell Degeneration 7 Jackson
Gene symbol: Agtpbp1
Strain of origin: C.129S2(B)- Igh-6tm1Cgn/J
Current strain name: C(Cg)-Agtpbp1pcd-7J/J
Stock #: 005501 (view JAX® Mice Data Sheet for additional information including Price and Supply Information) (NOTE- As of 2-1-2007 is available only as DNA from the Jackson Laboratory DNA Resource)
Phenotype categories: NeurologicalOrigin and Description
The Agtpbp1pcd-7J/J mutation was discovered by Andrea Snyder in a production colony of C.129S2 Igh-6tm1Cgn mice at the Jackson Laboratory in July 2003. Mice homozygous for this spontaneous, recessive mutation are recognizable by a moderate ataxia that begins at 3-4 weeks of age and becomes more intensified by 5 weeks of age. In addition to the ataxia, mutants present the severe deficiency of Purkinje cells characteristic of other Agtpbp1 alleles and live through adulthood.
Genetic Analysis
In order to determine the mode of inheritance, ovaries from a female homozygous for this new mutation were transplanted into C3SnSmn.CB17-Prkdcscid/J hosts which were then mated to an unrelated C57BL/6J male. No affected offspring were observed in the F1 generation produced from this mating (0 affected/25 born). Mice from this F1 generation were then mated together to produce F2s, and from this intercross both affected and unaffected animals were produced, showing that the mutation is recessive.
A direct test for allelism was set up by mating a heterozygous male from the BALB/cByJ-Agtpbp1pcd-3J/Jstock with 2 heterozygous females carrying this new mutation. This mating produced 2 litters in which 1 offspring was affected (1/11 animals born), proving the new mutation to be an allele of the Agtpbp1 gene. The chromosomal position of the Agtpbp1 gene is at the 37 cM position on Chromosome 13 (MGD 2005).
A concurrent linkage cross to CAST/Ei substantiated the positive test for allelism. Using tail tip DNAs from 21 mutant F2 progeny and our standard PCR protocols , we found no recombinants with D13Mit157, which is located at 36 cM on Chromosome 13.
Pathology
A routine pathological screen done on one homozygous and one heterozygous mouse at 9 weeks of age showed the Purkinje cell loss typical of Agtpbp1 mutants and the hippocampus appeared enlarged. The corpus callosum was absent in both mice, but this is a strain characteristic Of BALB/cJ mice and not caused by the mutation.
The results of auditory brainstem response (ABR) tests showed that two 5 - week old homozygous mutant mice and a heterozygous littermate all had normal hearing thresholds, but the response latency was longer for the homozygous mutants than for the heterozygote.
The eyes of 2 homozygous and 1 heterozygous mutant were examined by an opthalamoscope and found to be normal.
Discussion
We discovered and characterized a new remutation of the Agtpbp1 gene (pcd-7J). This remutation exhibits a similar clinical and histopathological phenotype to the original pcd mutation. A direct test for allelism with pcd-3J and the new mutation proved to be allelic.
Acknowledgements
The authors wish to thank Andrea Snyder for the discovery of the mutant, Norm Hawes for examination of the eyes, Heping Yu for hearing assessment, and Coleen Marden for her excellent technical assistance in preparing tissues for pathology.
References
MGD
Mouse Genome Database (MGD) Mouse Genome Informatics Project, The Jackson Laboratory, Bar Harbor, Maine. World Wide Web
