Quivering 10 Jackson and quivering 11 Jackson; two new remutations in the Spnb4 gene.
Authors: Belinda S. Harris, Chantal Longo-Guess, Leona Gagnon, Patricia F. Ward-Bailey 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) , Cancer Center Core Grant CA34196 and NIDCD/NIH grant DC04301 (KR Johnson, PI).
Mutation (allele) symbol: qv-10J; qv-11J
Mutation (allele) name: quivering 10 Jackson; quivering 11 Jackson
Gene symbol: Spnb4
Strain of origin: BALB/cJ (qv-10J) and C57Bl/6J (qv-11J)
Current strain name: BALB/cJ-Spnb4qv-10J; C57Bl/6J-Spnb4qv-11J
Stock #: 008521 (qv-10J); 008522 (qv-11J) (view JAX¨ Mice Data Sheets for additional information including Price and Supply Information)
Phenotype categories: neurological
Abstract
We have identified two new recessive remutations in the Spnb4 gene, qv-10J and qv-11J. Mice affected by these mutations have similar neurological phenotypes, including body tremor. For qv-10J, a direct test for allelism was performed and confirmed with the previously described quivering mutation (Spnb4qv), while allelism for qv-11J was proven by testing with qv-10J.
Origin and Description
The quivering 10 Jackson remutation was found at The Jackson Laboratory in the progeny of a BALB/cJ- ichq X C57BL/6J mating. Mice affected by the qv-10J mutation can be recognized by two months of age by a mild wobble and tremors in the hind end. This phenotype progressively worsens with age. The quivering 10 Jackson mutation has been maintained by a brother X sister mating scheme. Either homozygote female x heterozygous male matings or heterozygote x heterozygote matings (in either direction) are utilized. This mutation has been found to originate in the BALB/cJ parent. Unlike the original qv mutants that die at 5 months of age, most qv-10J mutants live a normal lifespan. Males carrying the qv-10J mutation appear to be sterile, but females do breed.
The quivering 11 Jackson remutation was identified by Marcus Boland in a C57BL/6J production colony. The mutant phenotype is visible by three weeks of age and includes a body tremor and an abnormal hind leg gait. The male mutant mice do not breed, so the quivering 11 Jackson colony is maintained by breeding a homozygous female to a heterozygous male. Quivering 11 Jackson mice appear to live a normal lifespan.
Genetic Analysis
Evidence for allelism : Two female mice homozygous for the quivering 10J mutation were mated to a heterozygote C3H/HeJ-qvlnd-2J/+ male mouse. This mating produced seven affected mice out of a total of 26 born proving allelism. Using standard mapping protocols some of the affected mice were confirmed by mapping to be in the same location (28.1-28.2 Mb) as the original quivering mutation on Chromosome 7. A female mouse homozygous for the quivering 10J mutation was mated to a heterozygous quivering 11 J male. This mating produced three litters totaling 14 mice, of which 8 were mutant, thus confirming allelism.
Pathology
A routine pathological screen of 3 qv-10J mutants at 5 weeks of age, 1 at 6 weeks of age and two at 7 weeks of age showed no gross abnormalities, similar to the pathology of the original quivering mutation. The eyes of five mutants and two controls at five weeks of age were examined with an opthalamascope and were determined to be normal normal.
Hearing as assessed by auditory brainstem response (ABR) testing for both mutations revealed hearing impairment. Five qv-10J mutants at five weeks of age displayed severe hearing loss with no ABR detected at the highest intensities tested (100 dB SPL), while two controls at five weeks of age had normal hearing. Three qv-11J mutant mice were assessed for hearing between four and fourteen weeks. These mice displayed only slightly elevated hearing thresholds indicating hearing impairment, but not deafness. Interestingly, the ABR wave-form pattern for each mutation was different (Fig 1). Quivering 10 Jackson mice produced a wave pattern similar to the originally described quivering mutation (qv), consisting of only the first ABR peak, while quivering 11 Jackson mice produced a less aberrant pattern, indicating that the demyelination caused by the qv-11J mutation is probably not as severe as that of qv and qv-10J. The quivering 11 Jackson allele retains all five peaks associated with a normal ABR click response (Fig 1 arrows); however, a decrease in amplitude and increase in latency is observable in the qv-11J traces when compared to the control.
Acknowledgements
The authors would like to thank Norm Hawes for eye examinations, Rod Bronson for pathology evaluation, Sandra Gray for qv-11J colony development and Coleen Marden for tissue preparation.
