Study Of The Expression And Relative Functions Of CyclinA1 In Multi-organs

CyclinA1 is an important member of cyclin family regulating the cycles in cell mitosis or meiosis. An interesting aspect about cyclin A is that there are both an embryonic and a somatic form of the protein. Organisms exemplified by Dro-sophila contain a single essential cyclin A gene. Other organisms such as Xeno-pus , mice and human contain two A - type cyclins an embryonic - specific cyclin Al and a somatic cyclin A2. Cyclin Al is only expressed in meiosis and very early embryos, whereas cyclin A2 is present in proliferating somatic cells. The only essential function of cyclin A1 in mice appears to be in spermatogenesis. In contrast, cyclin A2 is essential, and disruption of its gene causes early embryonic lethality.Recent studies found that high level expression of cyclinAl in acute mye-loid leukemia, testis cancer and et al. This proposed that cyclinAl was involved not only in normal organs and tissue but also pathological procedure. Its function might be not that limited as that had been reported.Why can not mature sperms be produced without functional cyclinAl? Who does lead those cells to apoptosis? To answer this question, p53 mutant mice and cyclinAl mutant mice were crossed to generate four groups of male litterma-tes with different genetic background, p53 mutant, cyclinAl mutant and double mutant. The development and apoptosis of male germ cells were analyzed by TUNEL staining. To find out covert or delayed phenotype of mice with mutant cyclinA1, we keep housing and observing mutant and wild type mice longer than 9 months and observed their skin on head and neck. Immunohistochemical staining was applied to test cyclinAl expression in skin. On the largest cross section of testes, cyclinAl mutant group presented 348 ± 104 apoptotic cells, which was obviously higher than 121 ±38, that of double mutant group, t =3.2579,P =0.0472. p53 mutant group presented the least, 45 ±24 apoptotic cells. Matched pair t - test showed very significant difference, t=8.4013, P=0.0035. At the same time among those mice being fed and observed for a long time-, specific skin lesions on head and neck occurred in 11 of the 46 mice with mutant cyclinAl. In skin lesions and their margins, pathological examination found hyper-keratosis of epiderm and hypertrophy of sebaceous gland . However there was no similar skin lesion in 25 wild type mice. By immunohistochemical examination with specific antibody of cyclinAl, we found positive staining in the sebaceous gland of wild type specimen but not in cyclinAl mutant mice. Our study suggests , p53 - dependent apoptosis pathway may be an effector of cellular proofreading that acts to maintain the cellular integrity of germ cells during spermato-genesis. CyclinAl might also be involved in the normal function maintain of sebaceous gland, though not exclusive or always necessary.The results above brought up a hypothesis, " Dose cyclinAl function in germinal layer of skin at the early stage of life when cells there divide and proliferate actively?" We also observed that female mice with mutant cyclinAl delivered less littermates than wild type mice did. What is the real reason of this phenomenon? Skin around left ear and ovaries were selected to check the expression of cyclinAl. Our data showed, the expression of cyclinAl could be found both in germinal layer of skin and several developing eggs. The expression level seems relative to the activity of cell division and proliferation. CyclinAl positive eggs have characteristics matching the case of developing eggs before ovulation, small number, big size and superficial distribution.In conclusion, focusing on the expression and functions of cyclinAl, the mechanism of male germ cell apoptosis induced by cyclinAl mutation was studied. Furthermore, we were the first group reporting the specific skin lesion induced by cyclinAl mutation on head and neck, and its onset, clinical manifestation, the general outlook and histopathological variation. It was also the first time to observe cyclinAl expression in germinal layer and sebaceous gland of skin, so that the important role of cyclinAl maintaining normal morphology and function of skin was noticed. Moreover, the expression of cyclinAl in developing eggs was reported for the first time, which provided a novel research direc-...