Accelerated intestinal transit in inbred mice with an increased number of interstitial cells of Cajal.

The interstitial cells of Cajal (ICC) play an important role in coordinating intestinal motility, and structural alterations in ICC are found in several human digestive diseases. Mouse models with defects in ICC allow a better understanding of their functions. We investigated the pattern of intestinal motility and the distribution of ICC in the PRM/Alf inbred mouse strain, characterized by a selective intestinal lengthening. In PRM/Alf mice, the digestive transit time, evaluated by using thermophilic Bacillus subtilis spores, was normal, indicating accelerated transit. The contractility and slow-wave frequency, recorded on isolated segments from the proximal small intestine, were significantly increased. The number of ICC was also significantly higher along the small intestine and the colon. The concomitant increase of the contractility, the slow-wave frequency, and the number of ICC is consistent with the proposal of a role of ICC number increase in the higher intestinal transit speed. The PRM/Alf model should be useful to further investigate the roles of ICC in the control of digestive motility.

Twister mutant mice are defective for otogelin, a component specific to inner ear acellular membranes.

Deafness is a common sensory defect in human. Our understanding of the molecular bases of this pathology comes from the study of a few genes that have been identified in human and/or in mice. Indeed, deaf mouse mutants are good models for studying and identifying genes involved in human hereditary hearing loss. Among these mouse mutants, twister was initially reported to have abnormal behavior and thereafter to be deaf. The recessive twister (twt) mutation has been mapped on mouse Chromosome (Chr) 7, homologous to the long arm of human Chr 15 (15q11). Otog, the gene encoding otogelin, a glycoprotein specific to all the acellular membranes of the inner ear, is also localized to mouse Chr 7, but in a region more proximal to the twister mutation, homologous to the short arm of human Chr 11 (11p15) carrying the two deafness loci, DFNB18 and USH1C. Mutant mice resulting from the knock-out of Otog, the Otog(tm1Prs) mice, present deafness and severe imbalance. Although twt had been mapped distally to Otog, these data prompted us to test whether twt could be due to a mutation in the Otog locus. Here, we demonstrate by genetic analysis that twt is actually allelic to Otog(tm1Prs). We further extend the phenotypical analysis of twister mice, documenting the association of a severe vestibular phenotype and moderate to severe form of deafness. Molecular analysis of the Otog gene revealed the absence of detectable expression of Otog in the twister mutant. The molecular and phenotypical description of the twt mouse mutation, Otog(twt), reported herein, highlights the importance of the acellular membranes in the inner ear mechanotransduction process.