Cerebellar purkinje cell loss during life span of the heterozygousStaggerer mouse (Rora+/Rorasg) is gender-related
✍ Scribed by Doulazmi, Mohamed; Fr�d�ric, Florence; Lemaigre-Dubreuil, Yolande; Hadj-Sahraoui, Nadia; Delhaye-Bouchaud, Nicole; Mariani, Jean
- Book ID
- 101220824
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 264 KB
- Volume
- 411
- Category
- Article
- ISSN
- 0021-9967
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✦ Synopsis
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 ϩ /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 (ϩ/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 ϩ /Rora sg and in their Rora ϩ /Rora ϩ littermates at 1, 3, 9, 13, 18, and 24 months of age. In the Rora ϩ /Rora ϩ , 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 ϩ /Rora ϩ males had slightly more PC than females. In the Rora ϩ /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 ϩ /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 ϩ /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.