Previous work demonstrated a role for nonmuscle myosin heavy chain (NMHC) II-B during mouse brain development. Mice carrying a point mutation in NMHC II-B (R709C) demonstrated decreased migration of cerebellar granule cells, pontine neurons and facial neurons. Due to the presence of the Neo-r cassette in an intron, these mice expressed decreased quantities of the mutant protein (25% of the amount of protein expressed by the wild-type mouse). Removing this cassette by crossing hypomorphic mice with mice expressing Cre-recombinase restored normal expression of the mutant allele and also generated a new phenotype. These mice (B-C/B-C) developed focal disruptions of the cortical basement membrane as early as E12. At the disrupted areas, clusters of a neural cell mass abnormally protruded into the marginal zone between the neuroepithelium and the pia-meninges, resembling type II cobblestone lissencephaly. Interestingly, these abnormalities were not seen in NMHC II-B ablated mice, indicating that these defects were not due to a loss-of-function of NMHC II-B. Since the defect was only seen in homozygous mutant mice, the mutant NMHC II-B could not be affecting the normal function of wild-type II-B. This suggests that mutant NMHC II-B interfered with the function of other members of the NMHC II family. Immunostaining using specific antibodies demonstrated that, whereas NMHC II-A and II-B were expressed, NMHC II-C was not expressed to a significant extent in the area around the basement membrane. Moreover, no NMHC II-C was found in meningeal fibroblast cells, which secrete a major component of cortical basement membrane. We postulate that the R709C mutation in NMHC II-B results in focal disruption of the cortical basement membrane because of its dominant negative effect on NMHC II-A
