alexa Cerebellar cell degeneration in the leaner mutant mouse.
Biomedical Sciences

Biomedical Sciences

Biology and Medicine

Author(s): Herrup K, Wilczynski SL

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Abstract Leaner is an autosomal recessive mutation of the mouse which results in a severe ataxia accompanied by cellular losses in the cerebellar cortex. The purpose of this report is to construct a developmental profile of these losses. Of the three cerebellar cell types studied, the granule cells are the first to show obvious degenerative changes. Pycnotic cells are numerous in the internal granule cell layer at postnatal day 10, and, while they are found throughout the cortex, they are more concentrated in the anterior folia. Initially, there is a strong tendency for the pycnotic cells to be located in the deep half of the internal granule cell layer. By four postnatal months the rate of loss has slowed but the finding of occasional pycnotic cells in animals up to one year old suggests it continues for the life of the animal. Quantitative analysis of Purkinje and Golgi cells in leaner cerebella reveals a progressive loss of these cells as well. The number of Golgi cells falls uniformly to around half of the wild-type number. By contrast, the Purkinje cells show much more extensive degeneration. Further, the rate of cell death shows a regional variation; it is significantly more rapid in anterior folia. Overall, the number of Purkinje cells in leaner falls to about one-fifth of the wild-type number. The loss of both Purkinje and Golgi cells occurs late relative to the major events of cerebellar maturation. Significant cell loss is not observed until the end of the first postnatal month. For the next 4 to 6 weeks there is extensive cell death but, rather than abating, it appears to continue at a low rate for the life of the animal. It is hoped that this developmental sketch of the leaner defect will stimulate others to approach leaner and its alleles, tottering and rolling, as models for heterogeneity of disease expression.
This article was published in Neuroscience and referenced in Biology and Medicine

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