Rostral cerebellar malformation (rcm/rcm): a murine mutant to study regionalization of the cerebellum.

A recently described recessive mouse mutant, rostral cerebellar malformation (rcm/rcm), demonstrates a swaying gait at approximately 12 days of age (Lane et al. [1992] J. Hered. 83:315-318). The mutant cerebellar (Cb) phenotype consists of cerebellar tissue that extends rostrally, beyond the usual distinct anterior cerebellar boundary, into the midbrain (Lane et al. [1992] J. Hered. 83:315-318; Ackerman et al. [1997] Nature 386:838-842). Interestingly, the cerebellar ectopia occurs in the absence of any significant alterations in the distribution of nuclear groups within the brainstem. The ectopic Cb tissue is 1) adherent to the posterior and lateral aspects of the inferior colliculus and to the lateral aspect of the rostral brainstem and 2) contains acellular regions within the inner granular layer (igl) and ectopic, calbindin-immunoreactive Purkinje cells (PCs) deep to the igl. Within the Cb proper, PC organization, as revealed by zebrin II immunoreactivity, is generally normal. In the ectopic Cb tissue PCs also exhibit a banded zebrin distribution. Analysis of the spinocerebellar projection in the mutant suggests a lobular distribution similar to that seen in the normal mouse. Within the anterior region, however, the normal parasagittal banding pattern is somewhat obscured. Spinocerebellar innervation of the ectopic Cb tissue exists, but it is almost exclusively to the region adjacent to the caudal inferior colliculus. In conjunction with the recent finding that the mutation appears to affect a UNC-5-like receptor protein for netrin-1, a molecule that may be involved in axonal guidance and cell migration (Ackerman et al. [1997] Nature 386:838-842), our results suggest that this mutant is an important model for the analysis of cerebellar development and regionalization.