The microtubule-associated protein astrin transgenesis rescues spermatogenesis and renal function in hypogonadic (hgn/hgn) rats.
The microtubule-associated protein astrin transgenesis rescues spermatogenesis and renal function in hypogonadic (hgn/hgn) rats.
复制标题
微管相关蛋白 astrin 转基因可挽救性腺功能减退 (hgn/hgn) 大鼠的精子发生和肾功能。
DOI：
10.1111/j.2047-2927.2012.00032.x
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Suzuki H.
中科院分区：
文献类型：
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作者：
Katayama K;Yasuda H;Tochigi Y;Suzuki H.
雄性性腺功能减退（hgn/hgn）大鼠表现为雄性不育、雌性生育能力下降、进行性肾功能不全和身体发育迟缓。这些缺陷与astrin的功能丧失突变有关，似乎与胚胎和出生后早期发育期间异常细胞增殖和细胞死亡增加导致的器官发育不全有关。由于小鼠spag 5（astrin直系同源物）的靶向破坏已被报道显示没有表型，我们进行了救援实验的基础上引入大鼠astrin cDNA转基因到hgn/hgnrats，以确定是否astrin实际上是必要的建立正常的男性生育力和肾功能。将Astrin转基因（Tg）大鼠与HGN品系的hgn/+大鼠交配，然后将Tg-hgn/+大鼠杂交以获得Tg-hgn/hgn。Tg-hgn/hgn男性表现出身体生长、生育能力和肾功能的恢复。这些转基因动物的睾丸尺寸小于正常对照组，但与hgn/hgn雄性动物相比增加了16.5倍。Tg‐hgn/hgn睾丸发生精子发生，其辅助生殖器官大小接近正常。hgn/hgn雄性动物表现为高促性腺激素性性腺功能减退。Tg‐hgn/hgn血清中睾酮水平升高和LH水平降低表明Leydig细胞功能恢复。Tg‐hgn/hgn雄性动物表现出正常的生殖行为，它们与Tg‐hgn/hgn雌性动物交配产生的幼崽具有正常的窝仔数。肾体积和肾小球数目完全恢复，肾功能生化指标正常。这些结果表明，转基因在睾丸和肾脏发育以及身体生长中具有功能。总之，astrin是必要的，以建立正常的大小（细胞数量）和功能的睾丸和肾脏在大鼠。
Male hypogonadic (hgn/hgn) rats show male sterility, reduced female fertility, progressive renal insufficiency and body growth retardation. These defects are associated with loss‐of‐function mutation of astrin and appear to be related to organ hypoplasia resulting from abnormal cell proliferation and increased cell death during embryonic and early postnatal development. As targeted disruption of mouse spag5 (astrin ortholog) has been reported to show no phenotype, we performed rescue experiments based on the introduction of rat astrin cDNA transgene intohgn/hgnrats to determine whether astrin is actually necessary for the establishment of normal male fertility and renal function. Astrin transgenic (Tg) rats were mated withhgn/+ rats of the HGN strain, and Tg‐hgn/+ rats were then crossed to obtain Tg‐hgn/hgn. Tg‐hgn/hgnmales showed recovery of body growth, fertility and renal function. Testis size was smaller in these transgenic animals than normal controls, but showed an increase by 16.5‐fold compared withhgn/hgnmales. Spermatogenesis occurred in Tg‐hgn/hgntestes, and their accessory reproductive organs were of approximately normal size.hgn/hgnmales show hypergonadotropic hypogonadism. Increased testosterone and decreased LH levels in Tg‐hgn/hgnserum indicated the recovery of Leydig cells' function. Tg‐hgn/hgnmales showed normal reproductive behaviour, and their mating with Tg‐hgn/hgnfemales produced pups in normal litter size. Their renal sizes and glomerular numbers showed complete recovery, and renal function assayed by biochemical parameters was normal. These results indicated that the transgene is functional in the testis and kidney development as well as body growth. In conclusion, astrin is necessary for the establishment of normal size (cell number) and function of the testis and kidney in rats.