ROSTRAL CEREBELLAR MALFORMATION (RCM RCM) - A MURINE MUTANT TO STUDY REGIONALIZATION OF THE CEREBELLUM/

A recently described recessive mouse mutant, rostral cerebellar malfor mation (rcm/rcm), demonstrates a swaying gait at approximately 12 days of age (Lane et al. [1992] J. Hered. 83:315-318). The mutant cerebell ar (Cb) phenotype consists of cerebellar tissue that extends rostrally , beyond the usual distinct anterior cerebellar boundary, into the mid brain (Lane et al. [1992] J. Hered. 83:315-318; Ackerman et al. [1997] Nature 386:838-842). Interestingly the cerebellar ectopia occurs in t he absence of any significant alterations in the distribution of nucle ar groups within the brainstem. The ectopic Cb tissue is 1) adherent t o 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-i mmunoreactive Purkinje cells (PCs) deep to the igl. Within the Cb prop er, PC organization, as revealed by zebrin II immunoreactivity, is gen erally normal. In the ectopic Cb tissue PCs also exhibit a banded zebr in distribution. Analysis of the spinocerebellar projection in the mut ant suggests a lobular distribution similar to that seen in the normal mouse. Within the anterior region, however, the normal parasagittal b anding pattern is somewhat obscured. Spinocerebellar innervation of th e ectopic Cb tissue exists, but it is almost exclusively to the region adjacent to the caudal inferior colliculus. In conjunction with the r ecent finding that the mutation appears to affect a UNC-5-like recepto r protein for netrin-1, a molecule that may be involved in axonal guid ance and cell migration (Ackerman et al. [1997] Nature 386:838-842), o ur results suggest that this mutant is an important model for the anal ysis of cerebellar development and regionalization. (C) 1998 Wiley-Lis s Inc.