1.小脳性失調症と雄性不妊を合併する新しい動物モデル: Ataxia and Male Sterilityマウス

概要

論文の詳細を見る
A novel genetic variant mouse, which exhibited ataxia and male sterility named AMS mouse, arising in autoimmune-prone MRL/lpr is described. Inheritance pattern of mutation and linkage between ams and lpr genes: The phenotype expression of the AMS trait was transmitted as autosomal recessive inheritance according to the Mendelian pedigree patterns. Analysis of the linkage between lpr and ams genes using littermates from the crosses of ams-lpr heterozygous mice indicated that the two autosomal recessive genes are inherited without linkage. Behavioral phenotype expression of the ams mutation: Qualitative observation of the spontaneous behavior and stance revealed subtle tremor of the whole body, difficulty in maintaining normal posture and moderate ataxia. The rotor rod test confirmed the presence of altered motor coordination based on the inabililty of the mutant mice to walk on the rod. Walking tracks of affected ams mutant illustrated an abnormal pattern of footfalls indicative ataxic gait. Stride lengths of steps were shorter than those of non-affected mice and the stride widths were a little bit wider when they were compared to the non-affected mice. Neuroanatomical expression of the AMS phenotype: Macroscopic examination of the brain showed a smaller cerebellum when it was compared to the age-matched unaffected mice. Microscopically, the cerebellar cortex retained its trilaminar organization and the formation of the anterior and posterior lobes, although loss of Purkinje cells (PCs) was observed throughout the Purkinje cell layer (PCL) . Anti-IP3R immunostaining of the cerebelli of 3-week old mice revealed an uneven staining of the PC and molecular layers due to profound degeneration and loss of the PCs. Examination of the time course of cellular loss in the PCL indicated that 50% of the PCs were already lost at 3 weeks of age, when the subtle manifestation of ataxia was first discernible. The cell loss accelerated very rapidly and was virtually complete at 6 weeks of age. There was no particular pattern of cell loss, rather the degeneration and loss of PCs seemed to take place in a single cell basis but the exact mechanism remains to be elucidated. The post-developmental onset of PC degeneration offers the advantage of looking at epigenetic factors that might alter the progression of the disease and therefore may help in the development of treatment strategies for human hereditary disorders. AMS phenotype expression in reproductive organs: The homozygous male and female mice were infertile. The male sterility was due to cessation of differentiation and degeneration of gametes mainly in spermatid stages after 5 weeks of age. As expected, the tubes in the epididymis appeared almost empty or contained minimal amount of degenerating sperms. In addition, there were no pathological changes in the hypothalamus, pituitary gland, Leydig and Sertoli cells indicative of a hormonal defect. These findings suggest that pretesticular causes did not contribute to the male sterility. On the other hand, histopathological examination of the ovaries showed no major changes and the ova were fertile in in vitro fertilization. Effect of ams mutation on immune system: In addition to the two major manifestations in the central nervous system and male reproductive system described above, the ams mutation was associated with a reduction of the spleen weight by about 45% when it was compared to the lpr non-homozygous mice. Immune cytological changes were also evident in the spleen. However, changes in the immune system did not result in clinically overt immunological diseases as immunodeficiency or autoimmunity, and interpreted as a minor effect of ams mutation. Conclusion: A new mutant mouse manifesting ataxia and male sterility was described. This mutant might help us understand the mechanisms of neurodegenerative processes and male sterility as well as the common genetic

1.小脳性失調症と雄性不妊を合併する新しい動物モデル: Ataxia and Male Sterilityマウス

スポンサーリンク

概要

論文 | ランダム

スポンサーリンク