| First Author | Zhou L | Year | 2006 |
| Journal | Proc Jpn Soc Animal Models Hum Dis | Volume | 22 |
| Pages | 19-25 | Mgi Jnum | J:278981 |
| Mgi Id | MGI:6360931 | Doi | 10.1538/expanim1992.22.19 |
| Citation | Zhou L, et al. (2006) Ataxia and male sterility (AMS) mutant mouse. An analysis of the ams mutation and the different types of cell death affected by this mutation. Proc Jpn Soc Animal Models Hum Dis 22:19-25 |
| abstractText | The Ataxia and Male Sterility (AMS) mouse is a mutant that exhibits ataxia due to a near-complete loss of the cerebellar Purkinje cells and male sterility because of severe oligospermia due to the degeneration and death of differentiating germ cells in the seminiferous tubules. The disease-responsible ams gene was shown to be allelic to Nna1, of which the classical mutation, pcd, has been shown by others to be a severe allele for the Purkinje Cell Degeneration mouse, by mating heterozygous pairs from each mutant strain . A RT-PCR analysis to sequentially cover the whole transcript of the Nna1 gene revealed that no obvious differences in either the size or quantity of the mRNA. By sequencing the cDNA base pairs a point mutation of G to C was detected at 2423rd by in exon 17. This missense mutation caused 808th arginieproline and it appeared to affect the protein structure and stability, because the transfection of the cDNA construct of the wild-type, but not of the mutant, led to the translation and stable expression of the protein. To investigate how ams mutation affects the cellular processes, we devoted our efforts to the morphological analysis of the mode of cell death. We herein describe the different types of cell death in the AMS mouse. The causes of the acute pathological atrophy of the AMS cerebellum were not only the primary near-complete loss of the Purkinje cells but also the secondary damage to other cells. Dying Purkinje cells lacked the characteristics of classical apoptosis except for their light microscopic morphology, but their death was considered to be autonomous death triggered by the direct effect of the ams mutation, because of their acute and near-complete disappearance and the particular changes observed in the cytoplasm. In contrast, in the granular layer, typical apoptotic bodies were recognized by electron microscopy, and a substantial number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) -positive cells and activated caspase-3-positive cells were observed. Granule cell death was considered to be target-related apoptosis which was induced after post-synaptic Purkinje cell death, because the age-dependent changes in the TUNEL-positive cell counts followed that of Purkinje cell loss and the peak value was still noted 1 week after the total loss of Purkinje cells. Our results indicate that both the total and partial losses of Purkinje cells and granule cells, respectively, contributed to the atrophy of the AMS cerebellum. Another study on the photic injury of the photoreceptor cell of the AMS retina revealed that the cells had lost the ability to resist such injurious factors while, in addition, the process of apoptotic cell death was also different from that of classical apoptosis. Since the ams mutation affects the dying process of many cell types in different manners, Nna1 is likely to act as an important regulator of the life of cells. |
