自发矮小症突变大鼠家系的建立及其主要生物学特性测定

Establishment of a rat model family with spontaneous short stature and identification of its main biological characteristics

目的 建立自发常染色体显性突变矮小症SD大鼠模型家系,测定其主要生物学特性数据。方法 将封闭群SD大鼠生产群中出现的矮小症突变个体扩群繁殖建立家系,统计后代中矮小症与正常个体的性状分离比例,鉴定其遗传模式;测定家系个体的体重、体尺,主要脏器重量及指数,血液生理(18项)生化(20项)等指标以及繁殖性能等数据,明确突变个体的表型特征及生物学特性。结果 建立了自发常染色体显性突变的矮小症SD大鼠封闭群家系,家系暂时命名为SSR;成年(12周龄)SSR体重分别为野生型的57%(♂)和65%(♀),差异极具显著(P<0.01);成年SSR体长、尾长、胫骨长、股骨长等体尺数据以及主要脏器(心、肝、脾、肺、肾、睾丸/卵巢)重量均显著低于野生型大鼠(P<0.01);成年SSR胫骨长、股骨长指数及主要脏器(心、肝、脾、肺、肾、睾丸/卵巢)指数与野生型之间无显著性差异(P> 0.05);成年雌性SSR生殖器官发育正常,但不排卵。结论 建立了能稳定遗传的自发常染色体显性突变的矮小症SD大鼠家系,可作为人类生长发育及生殖功能研究的动物模型。

Objective The aim of this study was to establish a rat model of spontaneous short stature associated with female infertility. The main biological characteristics of the rat model were then identified.Methods The pedigree of mutant individuals with a short stature in the production group of SD rats was established by expanding the population. The proportion of offspring of mutant individuals with a short stature and that of the normal individuals was calculated and the genetic model was identified. Weight, body size, weight and index of main organs, blood physiology(18 items), biochemistry(20 items), and reproductive performance of the mutant individuals were determined to clarify their phenotypic characteristics and biological characteristics.Results A family of SD rats with idiopathic autosomal dominant mutations was established, which was named SSR.Adult(12 weeks old) SSR rat weights were 57% of wildtype(♂)and 65%(♀),Very significant difference(P < 0.01).The body length, tail length, tibia length, femur length and other body size data of adult SSR and the weight of main organs(heart, liver, spleen, lungs, kidneys, testes/ovaries) were significantly lower than those of wild type rats(P < 0.01);There were no significant differences in the adult SSR rat shinbone length, femoral bone length index, or major organ indexes, compared with the wildtype(P > 0.05). Reproductive organ development of adult female rats was normal, but ovulation was not observed.Conclusions Spontaneous autosomal dominant mutations in dwarfism lines that can be stably inherited were established, which can be used as an applied study for human growth and infertility models. Female individuals were found to be infertile during the study, but further studies are needed to determine whether infertile individuals can have children.