Development of C57BL/6J-AgtKO mice

C57BL/6J-AgtKO 小鼠的发育

• 批准号: 09680826
• 负责人: FUKAMIZU Akiyoshi
• 金额: $ 1.92万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680826/
• 关键词: Angiotensinogen; knockout; Renin-angiotensin system; Hydronephersis; Blood-brain barrier; アンギオテンシンII; 高血圧; トランスジェニックマウス; 1型受容対; 2型受容対; アポトーシス; アンギオテンシノーゲン遺伝子欠損マウス; 腎; 実験動物

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.

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。

项目成果

Ishida, J.: "Angiotensinogen-Knockout Mice." Biochem.Biophys.Res.Commun.252. 610-616 (1998)

Ishida, J.：“血管紧张素原敲除小鼠”。

Yoshida E, Nakajima T, Murakami K, Fukamizu A.: "Identification of N-terminal minimal transactivation domain of CBP, p300 and caenorhabditis elegans homologues."Gene. 208. 307-314 (1998)

Yoshida E、Nakajima T、Murakami K、Fukamizu A.：“CBP、p300 和秀丽隐杆线虫同源物 N 末端最小反式激活结构域的鉴定。”基因。

Taniguchi K.,et al.: "Pathologic characterization of hypotensive C57BL/6J-agT:angiotensinogen-deficient C57BL/6J mice"Int.J.Mel.Med.. 1. 583-587 (1998)

Taniguchi K.,et al.：“低血压 C57BL/6J-agT 的病理特征：血管紧张素原缺陷的 C57BL/6J 小鼠”Int.J.Mel.Med.. 1. 583-587 (1998)

Ohshima T, Iwama M, Ueno Y, Sugiyama F, Nakajima T, Fukamizu A, Yagami K.: "Induction of apoptosis in vitro and in vivo by H-1 parvovirus infection."J.Gen Virol.. 79. 3067-3071 (1998)

Ohshima T、Iwama M、Ueno Y、Sugiyama F、Nakajima T、Fukamizu A、Yagami K.：“H-1 细小病毒感染在体外和体内诱导细胞凋亡。”J.Gen Virol.. 79. 3067-3071

Kakinuma Y.,et al.: "Impaired blood-brain barrier function in angiotensinogen-deficient mice"Nat.Med.. 4. 1078-1080 (1998)

Kakinuma Y.等人：“血管紧张素原缺乏小鼠的血脑屏障功能受损”Nat.Med.. 4. 1078-1080 (1998)