Carranza, Jose Yamada, Kazuki Sakae, Yuta Noh, Jongsung Choi, Man Ho Tanaka, Minoru 2024-06-28T06:30:23Z 2024-06-28T06:30:23Z 2024-06-28 2024-06 0289-0003 https://pubs.kist.re.kr/handle/201004/150125 cytochrome P-450, 21-hydroxylase (cyp21a2), encodes an enzyme required for cortisol biosynthesis, and its mutations are the major genetic cause of congenital adrenal hyperplasia (CAH) in humans. Here, we have generated a null allele for the medaka cyp21a2 with a nine base-pair insertion which led to a truncated protein. We have observed a delay in hatching and a low survival rate in homozygous mutants. The interrenal gland (adrenal counterpart in teleosts) exhibits hyperplasia and the number of pomca-expressing cells in the pituitary increases in the homozygous mutant. A mass spectrometry-based analysis of whole larvae confirmed a lack of cortisol biosynthesis, while its corresponding precursors were significantly increased, indicating a systemic glucocorticoid deficiency in our mutant model. Furthermore, these phenotypes at the larval stage are rescued by cortisol. In addition, females showed complete sterility with accumulated follicles in the ovary while male homozygous mutants were fully fertile in the adult mutants. These results demonstrate that the mutant medaka recapitulates several aspects of cyp21a2-deficiency observed in humans, making it a valuable model for studying steroidogenesis in CAH. English Zoological Society of Japan Genetic Disruption of cyp21a2 Leads to Systemic Glucocorticoid Deficiency and Tissues Hyperplasia in the Teleost Fish Medaka (Oryzias latipes) Article 10.2108/zs230107 1 Zoological Science, v.41, no.3, pp.263 - 274 Zoological Science 41 3 263 274 N scie scopus 001240951800004 2-s2.0-85194845665 Zoology Zoology Article CONGENITAL ADRENAL-HYPERPLASIA 21-HYDROXYLASE CORTISOL MODEL EXPRESSION PATHWAYS CAH 21-hydroxylase deficiency cortisol biosynthesis cyp21a2 Oryzias latipes