Cerebellar purkinje cell loss during life span of the heterozygous Staggerer mouse ( Rora + /Rora sg ) is gender‐related

The staggerer mutation causes dysgenesis of the cerebellar cortex in the homozygous mutant ( Rora sg /Rora sg ). The mutation acts intrinsically within the Purkinje cells (PCs), leading to cytological abnormalities and a severe deficit in the number of these cells. In contrast, in the heterozygous staggerer ( Rora + /Rora sg ), the cytoarchitecture of the cerebellar cortex appears to be normal, but quantitative studies have revealed a significant loss of cerebellar neurons with advancing age. In the heterozygous reeler ( +/rl ), another mutant presenting a PC loss with age, we have found that only males were affected (Hadj‐Sahraoui et al., 1996). In the present study, we have investigated whether a similar gender effect exists in the heterozygous staggerer during life span. PCs were counted on cerebellar sagittal sections in male and female Rora + /Rora sg and in their Rora + /Rora + littermates at 1, 3, 9, 13, 18, and 24 months of age. In the Rora + /Rora + , the number of PCs remained stable until 18 months, but there was a 25% significant loss in 24‐ month‐old mice of both genders. During life span, Rora + /Rora + males had slightly more PC than females. In the Rora + /Rora sg of both genders, the deficit in PC number was similar at 13 months but it appeared earlier in males, beginning between 1 and 3 months, and was aggravated regularly up to 13 months. By contrast, the decline was delayed and more abrupt in Rora + /Rora sg females, from a value still normal at 9 months to its maximal extent at 13 months. In view of these results, the heterozygous ( Rora + /Rora sg ) mouse offers an interesting model to test the interaction between sex, age, and genetic background on the development and maintenance of cerebellar neuronal populations. J. Comp. Neurol. 411:267–273, 1999. © 1999 Wiley‐Liss, Inc.