Genetic mapping of the whirler mutation

Abstract

The whirler (wi) mutation on mouse Chromosome (Chr) 4 results in an autosomal recessive neuroepithelial deafness and vestibular dysfunction exhibited as a characteristic shaker-waltzer behavior (deafness, circling, and head-bobbing). We have constructed a genetic linkage map across the wi region in both an interspecific [(wi/wi x CAST/Ei)F1 x wi/wi] backcross (n = 817) and an intraspecific [(wi/wi x CBA/Ca)F1 x wi/wi)] backcross (n = 335). In the interspecific backcross, wi was found to be non-recombinant with Orm1, 0.12 cM distal of D4Mit87 and Ambp, and 0.12 cM proximal of CD301. In the intraspecific backcross, wi was found to be non-recombinant with Orm1 and D4Mit244, 0.3 cM distal of Mup1, and 0.6 cM proximal of Tnc. We also report a family from the interspecific backcross that shows evidence of multiple recombinations across the region of mouse Chr 4 around the wi locus. These rearrangements appear specific to both the region and the family.

Essential role of BETA2/NeuroD1 in development of the vestibular and auditory systems

“…BETA2/NeuroD1 is expressed in sensory organs such as the eye (Morrow et al 1999), olfactory bulb (Lee et al 2000) and the inner ear (this study). As circling behavior is a characteristic of mouse mutants with inner ear defects (Gibson et al 1995;Bussoli et al 1997;Rogers et al 1999), we first examined the hearing abilities of the BETA2/NeuroD1 null by measuring the auditory brainstem responses (ABR) evoked by acoustic transients (clicks). The ABR consists of multiple waves: Wave 1 is believed to reflect activation of the primary afferent nerve terminals in brainstem nuclei, and wave 2 reflects activation of the cochlear nuclear complex (Mitchell and Clemis 1977).…”

DFNB31, a recessive form of sensorineural hearing loss, maps to chromosome 9q32-34

“…The region syntenic to the DFNB31 interval is located on the murine chromosome 4, 31 cM from the centromere. It contains the locus of the recessive mutant whirler (wi), 14,15 which is characterised by profound deafness and vestibular dysfunction. Therefore, it is reasonable to propose that DFNB31 and whirler may represent defects of the same gene.…”

Abnormal circling behavior in rat mutants and its relevance to model specific brain dysfunctions

“…Indeed, in addition to lateralities in striatal dopaminergic function as a cause for rotational behavior in rats, circling is often observed in mouse and rat deafness mutants and is commonly suggested to be a consequence of inner ear defects impairing vestibular functions (Lyon and Searle, 1989;Kitamura et al, 1991;Bloom and Hultcrantz, 1994;Truett et al, 1994;Brock et al, 1995;Alagramam et al, 1999;Rogers et al, 1999;Kaiser et al, 2001;Smits et al, 2005;Friedman et al, 2007). The morphologic patterns of the genetically induced bilateral degeneration of the vestibular neuroepithelium observed in such mutants include complete sensory hair loss, protrusions of the cytoplasm and disintegration of the cuticular plate, disarray of stereocilia, sensory hair fusion, and the formation of intracellular vacuoles.…”