title: A new spontaneous mutation in the mouse Ames waltzer gene, Pcdh15.
abstract: A recessive deafness mutation in the mouse arose spontaneously and was identified in a colony segregating a null allele of the gastrin-releasing peptide receptor (Grpr) locus. Auditory-evoked brain stem response measurements revealed deafness in 7-week-old affected mice. By linkage analyses, the mutant phenotype was mapped near marker D10Mit186 and the protocadherin gene Pcdh15. As shown by complementation testing, the new mutation is allelic with Ames waltzer (Pcdh15(av)). Sequencing mutant-derived brain Pcdh15 cDNAs identified the insertion of a cytosine residue at nucleotide position c2099 (2099insC), which results in a frame-shift and premature stop codon. Abnormal stereocilia on inner and outer hair cells of the organ of Corti were identified by scanning electron microscopy as early as postnatal day 0 and cross-sectional histology revealed severe neuroepithelial degeneration in cochleas of 30-50-day-old mutants. The new allele of Ames waltzer, designated Pcdh15(av-Jfb), may aid in studying the histopathology associated with Usher syndrome type 1F, which is caused by a functional null allele of PCDH15.
authors.affiliation: G-Protein Coupled Receptors Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Lori L
authors.initials: LL
authors.lastname: Hampton
authors.forename: Charles G
authors.initials: CG
authors.lastname: Wright
authors.forename: Kumar N
authors.initials: KN
authors.lastname: Alagramam
authors.forename: James F
authors.initials: JF
authors.lastname: Battey
authors.forename: Konrad
authors.initials: K
authors.lastname: Noben-Trauth
mesh_terms: D000818:Animals; D001309:Auditory Threshold; D001483:Base Sequence / Q000235:genetics; D001522:Behavior, Animal / Q000502:physiology; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics*; D003051:Cochlea / Q000294:innervation / Q000473:pathology; D003596:Cytosine; D003638:Deafness / Q000235:genetics* / Q000473:pathology; D016057:Evoked Potentials, Auditory, Brain Stem; D016368:Frameshift Mutation / Q000235:genetics*; D005808:Genes, Recessive; D005816:Genetic Complementation Test; D008040:Genetic Linkage; D051379:Mice; D008815:Mice, Inbred Strains; D009069:Movement Disorders / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011498:Protein Precursors / Q000235:genetics*; D013136:Spiral Ganglion / Q000473:pathology
chemical_list: C418976:CDHR15 protein, mouse; D000070585:Cadherin Related Proteins; D015820:Cadherins; D011498:Protein Precursors; D003596:Cytosine