These mice carry an ENU-induced mutation characterized by circling behavior, head tilt and tossing, and deafness.
The Jackson Laboratory cannot guarantee that cryorecovery of strains from the discontinued NIH-funded Neuroscience Mutagenesis Facility (NMF) will be successful or that the anticipated phenotype or genotype will be obtained. The cryorecovery fee for this effort will not be refunded or prorated if the recovery is unsuccessful or is in any way unsatisfactory. Genotyping will be the responsibility of the Purchaser.Read More +
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. 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.
Complementation tests between NMF19 and Pcdhav-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.
This phenotypic deviant was generated by ethylnitrosourea (ENU) mutagenesis in C57BL/6J males (Stock No. 000664), in the Neuroscience Mutagenesis facility at The Jackson Laboratory. Mutagenized males were crossed to C57BL/6J females; G3 descendants of the mutagenized males were selected for neurological impairment. The mutation is 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.
|Allele Name||Ames Waltzer 5 Jackson|
|Allele Type||Chemically induced (ENU)|
|Allele Synonym(s)||neuroscience mutagenesis facility, 19; NMF19; Pcdh15av-nmf19; Pcdh15nmf19|
|Gene Symbol and Name||Pcdh15, protocadherin 15|
|Strain of Origin||C57BL/6J|
|Molecular Note||RT-PCR and sequencing demonstrated that the coding sequence of exon 13 was spliced to exon 15 due to an A to G substitution of the splice donor sequence of exon 14.|