Quaking 2 Jackson, a remutation of the Quaking (Qk) gene on Chromosome 17 in the Mouse.
Belinda S. Harris, Patricia F. Ward-Bailey, Kenneth R. Johnson, Roderick T. Bronson, and Muriel T. Davisson
Source of Support: This research was supported by grants NIH/NCRR RR01183 to the Mouse Mutant Resource (M.T. Davisson, PI) and The Cancer Core Grant CA34196.
Mutation (allele) symbol: Qkqk-2J
Mutation (allele) name: quaking 2 Jackson
Gene symbol: Qkqk-2J
Strain of origin: BKS.Cg-m+/+Leprdb
Current strain name: BKS.Cg-m+/+Leprdb-Qkqk-2J/J
Stock #: 005089 (view JAX® Mice Data Sheet for additional information including Price and Supply Information)
Phenotype categories: neuromuscular
Abstract
We have identified a new allele of the Quaking gene (Qk) by a direct test for allelism. Affected progeny were produced when a quaking homozygote and a mouse heterozygous for the new mutation were mated together. The phenotype is similar to the original quaking (qk) mutation.
Origin and Description
The Qkqk-2J remutation was discovered by Fred Rumill, Jr. in 2003 in a production colony of diabetic mice of the strain BKS.Cg-m+/+Leprdb at The Jackson Laboratory. Mice homozygous for this spontaneous remutation are recognizable at about two weeks of age by their rapid tremors, which is similar to the original quaking mutation. Homozygous qk2J/qk2J mice from neither sex has been used for breeding, and it is not known whether or not they are able to reproduce. Homozygous mutants may live to adulthood but survival is variable. In order to determine the mode of inheritance, ovaries from a female, homozygous for this new mutation, were transplanted into C3SNSmn.CB17-Parkdcscid/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/33 born). Mice from this F1 generation were then mated together to produce F2s, and in this cross both affected and unaffected animals were produced showing that the mutation is recessive.
Genetic Analysis
A direct test for allelism was set up by mating a homozygous female from the original quaking strain B6C3Fe-a/a-Qkqk) to a male heterozygous for this new mutation. This mating produced two litters in which seven affected quaking progeny were produced out of fourteen progeny born, proving the new mutation to be an allele of Qk. Quaking is located on Chromosome 17 at the 5.9 cM position (MGI) or NCBIm33 position 9.7 Mb.
Pathology
Routine pathological screening of mutants and controls showed that 3 week old homozygotes had holes in the striatum of the cortex and cerebellum and also in the myelin of the spinal cord (See Photo). Controls were normal. This lesion is similar to that seen in the original quaking mutation. Hearing as assessed by Auditory brain stem response testing (ABR) showed abnormal pattern waves and normal thresholds on all four homozygous mutants tested. The hearing pattern observed was similar to the pattern observed with the original quaking mutants. The eyes of four female and two male qk2J /qk2J mutants were examined with an opthalamscope and were determined to be normal. Controls tested had normal eyes.
Discussion
We have a new remutation to the Quaking gene that arose on a diabetic background segregating for the coat color "misty". This remutation exhibits a similar clinical and histopathological phenotype to the original quaking mutation and has been proven to be allelic.
Acknowledgements
The authors would like to thank the following for their excellent technical expertise: Norm Hawes for examining the eyes, Heping Yu for hearing assessment, and
Coleen Marden for preparing the mice for pathological screening.
References
Mouse Genome Database (MGD) Mouse Genome Informatics Project, The Jackson Laboratory, Bar Harbor, Maine. World Wide Web (2005)
(URL:http://www.informatics.jax.org)
MGSC27.33c.1. Mouse Genome Sequencing Consortium
