Chinese Journal of Tissue Engineering Research ›› 2013, Vol. 17 ›› Issue (24): 4521-4528.doi: 10.3969/j.issn.2095-4344.2013.24.022
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Cai Bin, Fan Dong-sheng
Received:
2013-01-17
Revised:
2013-02-26
Online:
2013-06-11
Published:
2013-06-11
Contact:
Fan Dong-sheng, M.D., Chief physician, Professor, Researcher, Doctoral supervisor, Peking University Third Hospital, Beijing 100191, China
dsfan@sina.com
About author:
Cai Bin★, Master, Peking University Third Hospital, Beijing 100191, China
caibin@bjmu.edu.cn
Supported by:
National Natural Science Foundation of China, No. 81030019*, 30871359*; Beijing Natural Science Foundation, No. 7082099*, 7102161*; Doctoral Fund of Ministry of Education, No. 20100001110084*; Capital Medical Science and Technology Development Fund, No. SF-2009-III-34*
CLC Number:
Cai Bin, Fan Dong-sheng. Germline degradation of a mouse model of familial amyotrophic lateral sclerosis when breeding[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(24): 4521-4528.
2.1 不同代小鼠的生育情况 引进后的小鼠记为第0代,共8只,其中8周B6SJL SOD1G93A/+半合子雄性种鼠4只,8周B6SJLF1/J+/+雌鼠4只,按之前文献报道的方法进行合笼交配[16],经交配后所生产的小鼠记为第1代。 第0代小鼠交配后所生产的第1代小鼠共50只,离乳时存活40只,平均每胎生产4.55只小鼠,每只雌鼠平均可生产2.75胎,每只雌鼠全部生育期平均生产12.5只小鼠。第3代生产的小鼠数量即第4代小鼠开始下降,平均每胎生产3.78只小鼠(与第1代比较,t=2.518,P=0.021),每只雌鼠平均可生产2.25胎(与第1代比较,t=1.414,P=0.207),每只雌鼠全部生育期平均生产8.5只(与第1代比较t=3.703,P=0.01)。传至第7代时,每只雌鼠平均每胎仅能生产3.5只小鼠(与第1代比较t=2.495,P=0.025),每只雌鼠平均仅能生产1.5胎(与第1代比较:t=3.273,P=0.017),每只雌鼠全部生育期平均仅能生产5.25只小鼠,与第1代和第4代比较:t 值分别为5.385和2.672,P值分别为0.002和0.037,且用于保种的雌鼠一半以上无法怀孕。以上结果显示在保种过程中,小鼠的生殖能力逐渐下降。 分别对第0,3,6代小鼠的生育情况进行了对比,见表1和图1-3。"
2.2 不同代小鼠性别比及基因型变化情况 第1代、第4代、第7代小鼠的雌雄比分别为21∶19,16∶12, 6∶1,虽然χ2=4.878,P=0.087,3个样本的差异无显著性意义,但可以看出在保种过程中雄性小鼠在生产的小鼠中所占的比例有下降的趋势。而第1代、第4代、第7代小鼠中携带SOD1G93A基因的杂合子突变型小鼠与不携带该致病基因的纯合子野生型小鼠的比分别为19∶21,13∶15,3∶4,虽然χ2=0.09,P=0.956,3个样本的差异也无显著性意义,但也可以看出在保种过程中携带治病基因的阳性小鼠在所生产小鼠中所占的比例也在逐渐下降。由于雄性小鼠以及携带SOD1G93A基因的阳性小鼠比例的下降,而且小鼠的生殖能力也显著下降,因此在第七代小鼠中没能得到携带SOD1G93A基因的杂合子突变型雄鼠,而保种过程中需要B6SJL SOD1G93A/+半合子雄性小鼠与B6SJLF1/J+/+雌鼠进行交配,所以保种无法进行下去导致了实验室该品系转基因小鼠的保种失败。在保种过程中,每1代所生产小鼠的性别比例以及携带SOD1G93A基因的阳性小鼠所占的比例也发生了变化,见表1和图4-5。"
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