Generation and reproductive phenotypes of mice lacking estrogen receptor β
Generation and reproductive phenotypes of mice lacking estrogen receptor β
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DOI：
10.1073/pnas.95.26.15677
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发表时间：
1998-12-22
影响因子：
11.1
通讯作者：
Smithies, O
中科院分区：
文献类型：
--
作者：
Krege, JH;Hodgin, JB;Smithies, O
雌激素影响生殖组织的分化和维持，影响脂代谢和骨重建。到目前为止，已发现两种雌激素受体，ERα和ERβ。我们之前培育并研究了缺乏雌激素受体α的基因敲除小鼠，并报告了严重的生殖和行为表型，包括雄性和雌性小鼠完全不育，以及乳房组织缺乏发育。在这里，我们描述了通过在胚胎干细胞中同源重组将新霉素抗性基因插入到编码基因的外显子3中而产生缺乏雌激素受体β(ERβ-/-)的小鼠。缺乏这种受体的小鼠发育正常，在大体和组织学上无法区分年轻的成年和它们的幼崽。RNA分析和免疫细胞化学显示，ERβ/-小鼠的组织缺乏正常的ERβRNA和蛋白质。对年轻的、性成熟的雌性老鼠进行的繁殖实验表明，它们可以生育，表现出正常的性行为，但与野生型老鼠相比，它们的后代更少、更小。超数排卵实验表明，这种生育力的下降是卵巢效率下降的结果。突变的雌性乳房发育正常，乳汁分泌正常。年轻的、性成熟的雄性小鼠没有明显的异常，繁殖正常。老年突变男性表现出前列腺和膀胱增生的迹象，我们的结果表明ERβ是正常排卵效率所必需的，但对女性或男性的性别分化、生育或哺乳不是必需的。需要进一步的实验来确定ERβ在骨骼和心血管动态平衡中的作用。
Estrogens influence the differentiation and maintenance of reproductive tissues and affect lipid metabolism and bone remodeling. Two estrogen receptors (ERs) have been identified to date, ER alpha and ER beta. We previously generated and studied knockout mice lacking estrogen receptor alpha and reported severe reproductive and behavioral phenotypes including complete infertility of both male and female mice and absence of breast tissue development. Here we describe the generation of mice lacking estrogen receptor beta (ER beta -/-) by insertion of a neomycin resistance gene into exon 3 of the coding gene by using homologous recombination in embryonic stem cells. Mice lacking this receptor develop normally and are indistinguishable grossly and histologically as young adults from their littermates. RNA analysis and immunocytochemistry show that tissues from ER beta -/- mice lack normal ER beta RNA and protein. Breeding experiments with young, sexually mature females show that they are fertile and exhibit normal sexual behavior, but have fewer and smaller litters than wild-type mice. Superovulation experiments indicate that this reduction in fertility is the result of reduced ovarian efficiency. The mutant females have normal breast development and lactate normally. Young, sexually mature male mice show no overt abnormalities and reproduce normally. Older mutant males display signs of prostate and bladder hyperplasia, Our results indicate that ER beta is essential for normal ovulation efficiency but is not essential for female or male sexual differentiation, fertility, or lactation. Future experiments are required to determine the role of ER beta in bone and cardiovascular homeostasis.