Circling behavior by weaning age, deaf by 14 weeks of age; reduced grip strength.

The visible phenotype is characterized by circling behavior, head tilt and tossing detectable by weaning age (average age of onset 4.9 +/-1.8 weeks; n=68), and deafness by 14 weeks of age; these mutants might therefore be useful for studying neurobiological mechanisms related to Usher syndrome and deafness. Homozygotes are viable, but are poor breeders. Complementation tests between NMF19 and Pcdh^15av-3J (Ames waltzer; Cook and Lane: Re-mutation to Ames waltzer, Mouse Genome 1993; 91, 554) produced affected mice displaying the circling and head tossing behaviors associated with a mutation in Pcdh15 (Alagramam et al., 2001, Nat. Genetics), i.e. a heterozygous mating produced 17% affected mice (1/6; single litter), and a homozygous x heterozygous mating produced 50% affected mice (5/10; 2 litters), suggesting nmf19 to be allelic to Pcdh15. The same laboratotry characterized the nmf19 mutation as a base substitution (A--> G) in the consensus splice donor sequence linked to exon 14, which results in the skipping of exon 14 and the splicing of exon 13-15; for further details see Washington et al., 2005. Whole ear exam on one mutant revealed absence of otoconia. Standard pathology work-up and serial sections of ears were performed on two additional mutants (226 or 292 days of age). Serial sections revealed a loss of neurons in the spiral ganglia, as well as a loss of hair cells. The other tissues appeared normal.

View video

• Cryopreserved embryos (EM)