Extra-Adrenal Induction of Cyp21a1 Ameliorates Systemic Steroid Metabolism in a Mouse Model of Congenital Adrenal Hyperplasia

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461575
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Naiki Yasuhiro 国立研究開発法人国立成育医療研究センター, 内分泌代謝科, 医員 (20470007)
• Co-Investigator(Kenkyū-buntansha): Katsumata Noriyuki 独立行政法人国立成育医療研究センター研究所, 基礎内分泌研究室, 室長 (10260340) ; Fukami Maki 独立行政法人国立成育医療研究センター研究所, 分子内分泌研究部, 部長 (40265872)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 副腎皮質過形成症 / 遺伝子治療 / アデノウィルス随伴ウィルスベクター / 21水酸化酵素欠損症 / 11β水酸化酵素欠損症

Outline of Final Research Achievements

We examined whether transduction of murine Cyp21a1 in extra-adrenal tissues could rescue steroid metabolism in 21-OHD mice to develop a gene therapy for congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency (21-OHD). We injected an adeno-associated viral (AAV) vector containing Cyp21a1 into the thigh muscles of 21-OHD mice. Serum progesterone/DOC ratios were markedly reduced in all four animals at 4 weeks after injection. These results indicate that extra-adrenal induction of Cyp21a1 ameliorates steroid metabolism in 21-OHD mice. We also introduced Cyp21a1 gene using AAV vector containing Cyp21a1 into the adrenal glands of 21-OHD mice. Instead of muscle injection, serum progesterone/DOC ratios did not change at 4 weeks after injection.
We also evaluate the efficacy of induction CYP11B1 gene using AAV vector to the fibroblast CAH due to steroid 11beta-hydroxylase deficiency. The hydroxylation of steroid 11beta hydroxylase was not detected by this method.

Free Research Field

小児内分泌