Development of C57BL/6J-AgtKO mice

为了了解血管紧张素原基因的功能，我们曾利用基因打靶技术建立了肥胖小鼠模型。血管紧张素原缺陷型（AgtKO）小鼠采用混合C57 BL/6 J、CBA和ICR杂交遗传背景维持。因此，需要开发具有同质遗传背景的AgtKO小鼠。1)本研究以C57 BL/6 J为遗传背景，通过快速回交、体外受精、青春期前超数排卵等方法，培育出AgtKO（C57 BL/6 J-AgtKO）。2)我们证明了C57 BL/6 J-AgtKO小鼠在断奶前死亡。3)我们指出，C57 BL/6 J-AgtKO的死亡率可以通过在出生后7天内皮下注射生理盐水来降低，并且C57 BL/6 J-AgtKO在第14天发生肾积水。4)细胞凋亡诱导参与C57 BL/6 J-AgtKO肾积水的发展。5)我们还证明了肾积水是通过血管紧张素原基因的遗传拯救来预防的。6)此外，我们表明Agt基因是维持血脑屏障功能所必需的。

We previously developed hypotensive mice by gene-targeting technique to understand the function of angiotensinogen gene. The angiotensinogen-deficient (AgtKO) mice were maintained with mixed C57BL/6J, CBA, and ICR hybrid genetic background. Therefore development of AgtKO mice with homogeneous genetic background is needed. 1) We developed AgtKO with genetic background of C57BL/6J (C57BL/6J-AgtKO) by speedy backcrossing through in virtro fertilization, using pre-pubertal superovulation. 2) We demonstrated that C57BL/6J-AgtKO mice die before weaning. 3) We indicated that mortality in C57BL/6J-AgtKO can be reduced by hypodermic saline injection in the 7 days following birth and that C57BL/6J-AgtKO are developed hydronephrosis by day 14. 4) The apoptotic induction is involved in the development of hydronephrosis on C57BL/6J-AgtKO. 5) We also demonstrated that the hydronephrosis is prevented by genetic rescue of the angiotensinogen gene. 6) Furthermore we indicated that the Agt gene are required for functional maintenance of blood-brain barrier.