Smad4 条件基因敲除小鼠前庭终器形态学研究

目的研究Smad4条件基因敲除小鼠前庭终器形忿改变，探讨Smad4基因对于前庭发育的作用。方法利用建立的Smad4条件基测敲除小鼠模型．通过光镜观察Smad4（＋／＋）、Smad4（＋／-）与Smad4（-／-）三种基因型小鼠（0．5、1．5月龄）的球囊及囊斑、椭圆囊及囊斑、半规管及壶腹嵴、前庭神经节、内淋巴管与囊的形态结构、毛细胞的形态及排列缺失情况。通过扫描电镜观察球囊斑、椭圆囊斑和壶腹嵴的形态结构、毛细胞及纤毛的排列缺失情况。结果Smad4（-／-）小鼠个体及内耳明显小于Smad4（＋／＋）和Smad4（＋／-），而后面二者区别不大。所有小鼠的球囊及囊斑、椭圆囊及囊斑、半规管、前庭神经节、内淋巴管与囊的大小和结构正常，淋巴囊腔饱满，囊斑处的感觉上皮、耳石、毛细胞及纤毛排列整齐，没有发现明显的病变．三个基因型间没有差异。Smad4（-／-）小鼠壶腹嵴囊性变多且严重、后半规管壶腹嵴出现明显的副嵴、偶尔可见壶腹嵴感觉上皮空泡样变。壶腹嵴的毛细胞和支持细胞排列整齐，形态无明显改变，未见缺失。扫描电镜示球囊斑、椭圆囊斑、后、外、上半规管壶腹嵴正常，三个基因型之间没有差异。结论Smad4（-／-）小鼠的前庭终器有轻微病理改变，Smad4（＋／＋）与Smad4（＋／-）小鼠的前庭终器形态结构基本正常．表明Smad4对于前庭终器的发育影响可能不明显。

The morphological changes of vestibular endorgans in Smad4 conditional knockout mice

Objective To investigate morphological changes in the vestibular endorgans of Smad4 gene conditional knockout mice and to explore the influence of the Smad4 gene on vestibular development. Methods Taking advantage of the model of Smad4 gene conditional knockout mice, the morphosis of the hair cell , sacculus, macula sacculi, utriculus, macula utriculi, semicircular canal, crista ampullaris, Scarpa ganglion, endolymphatic duct and sac were observed by light microscope in three genotypes of Smad4 (+/+), Smad4 (+/-) and Smad4 (-/-) mice (postnatal 0.5 months, 1.5 months). The morphosis of the macula sacculi, macula utriculi, crista ampullaris, hair cells and stereocilia and kinocilium were also observed by scanning electron microscope. Results The size of Smad4(-/-) individuals and inner ears were obviously smaller than that of Smad4(+/+) and Smad4(+/-) mice. No distinctive pathological changes had occurred in hair cells, sacculus, macula sacculi, utriculus, osseous semicircular canals, macula utriculi, Scarpa ganglion cells, endolymphatic duct and sac in three mouse genotypes. In Smad4(-/-) mice, there were extensive and severe cystis degeneration in all cristae ampullaris. Obvious secondary cristae appeared in the post crista ampullaris. Vacuole changes in sensory cells of cristae ampullaris occurred now and then. Hair cells and supporting cells of cristae ampullaris arranged well without absence and morphological changes. Results from scanning electron microscope demonstrated a normal macula sacculi, macula utriculi and crista ampullaris. There was no obvious differentiation in three genotypes. Conclusion There is mild pathological changes in vestibular endorgans of Smad4 (-/-) mice while there is normal structure in vestibular endorgans of Smad4 (+/+) mice and Smad4(+/-) mice. This data indicates that the Smad4 gene may have no remarkable influence on development of vestibular endorgans in mice.