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.
Laboratoire de Neurobiologie du Développement, Institut des Neurosciences (UMR 7624 CNRS), Université P. & M. Curie, 75005 Paris, France.
M
M
Doulazmi
F
F
Frédéric
Y
Y
Lemaigre-Dubreuil
N
N
Hadj-Sahraoui
N
N
Delhaye-Bouchaud
J
J
Mariani
D000375:Aging; D000818:Animals; D002525:Cerebellar Cortex / Q000166:cytology / Q000254:growth & development; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000235:genetics / Q000254:growth & development*; D011689:Purkinje Cells / Q000166:cytology* / Q000502:physiology; D012727:Sex Characteristics; D013045:Species Specificity