International Mammalian Genome Society


The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

F30 Functional and Genetic Analyses of the Jerker (je) Mouse Mutant

Torrance K. Jackson and Konrad Noben-Trauth. Section on Murine Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland 20850

The jerker (je) mutant was first described by Grüneberg et. al. (1941) who obtained the mutant as a "dancing adult female mouse" from a mouse fancier in 19381. Jerker mutants can be distinguished from normal littermates by their erratic circling behavior, head tossing and hyperactivity at three weeks of age. Weaning age jerkers show no startle reflex and in electrophysiological tests 2-3 week old homozygotes fail to produce normal round window action potentials and cochlea microphonics indicating a severe auditory dysfunction2. Histological examinations of je/je inner ears by Doel (1955) and Steel (1983) demonstrated a degeneration of the organ of Corti and the spiral ganglion during the early postnatal development3,2. By scanning electronmicroscopy the first pathological changes were observed at P1 when the cuticular plate started to fold and stereocilia appeared partially fused. At P12 stereocilia on both outer and inner hair cells are significantly shortened, and the cuticular plates continues to disintegrate. Whereas the outer hair cells showed a distorted configuration, the inner hair cell bodies appeared normal. In 12-week-old animals, however, the organ of Corti is merely a mass of disorganized cells4.

The apparent failure of je/je mutants to establish and maintain a functional organ of Corti during the postnatal development suggests a critical role for je during late hair cell differentiation and maturation. To investigate the molecular mechanisms that control these events we sought to identify the je locus. In the first step following a positional cloning strategy we analyzed 700 meioses derived from two intersubspecific mapping crosses [(CAST/Ei x JE/Le - je/je) F1 x F1] and [(CZECH/Ei x JE/Le- je/je) F1 x F1] using a number of polymorphic markers. We fine mapped the je locus to a 2.0cM interval between the recombinant flanking markers D4Mit180 and D4Mit344 on the distal end of mouse Chromosome 4.

To explore the penetrance and the degree of expressivity of the auditory and vestibular defects, we crossed je onto different genetic backgrounds and performed auditory evoked brain stem response analyses (ABR) on 40-50 F2 progeny. In 12 week old homozygotes both auditory and vestibular phenotypes are fully expressed, cosegregate, and appear completely penetrant.

1Grüneberg, H., Burnett, J.B. & Snell, G.B. Proc. Natl. Acad. Sci. 27, 562-565 (1941).
2Steel, K.P. & Bock, G.R. Behav. Neurosci. 97, 381-391 (1983).
3Deol, M.S. Proc. Roy. Soc. 145, 206-213 (1955).
4Sjostrom, B. & Anniko, M. ORL. J. Otorhinolaryngol. Relat. Spec. 54, 220-228 (1992).

 


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