EARLY DETECTION OF MOUSE WOBBLER MUTATION - A MODEL OF PATHOLOGICAL MOTONEURON DEATH

THE mouse recessive mutation wobbler, carried by the C57BL/6J strain, is a naturally occurring model of motoneurone death. The gene is unkno wn and in the absence of predictive markers, mutants have to be diagno sed by phenotypic criteria at 4 weeks after birth. We localized the wo bbler gene to chromosome 11 at 0.98 +/- 1.1 cM from the glutamine synt hetase (Glns) gene. A polymorphic allele of the Glns gene was then int roduced into the congenic wobbler strain by intraspecific crossing. On e-quarter of the offspring expressed the same phenotypic mutation as t rue wobbler and were detectable by PCR, as they are homozygous for the wobbler-linked Glns allele. The new mutants exhibit motoneurone degen eration despite the new genetic background.