Journalartikel

Jahr der Veröffentlichung: 2024

Zeitschrift: International Journal of Molecular Sciences

Bandnummer: 25

Heftnummer: 10

ISSN: 1661-6596

eISSN: 1422-0067

Open Access Status: Gold

DOI Link: https://doi.org/10.3390/ijms25105062

Verlag: MDPI

Abstract: 
Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder impairing cortisol synthesis due to reduced enzymatic activity. This leads to persistent adrenocortical overstimulation and the accumulation of precursors before the blocked enzymatic step. The predominant form of CAH arises from mutations in CYP21A2, causing 21-hydroxylase deficiency (21-OHD). Despite emerging treatment options for CAH, it is not always possible to physiologically replace cortisol levels and counteract hyperandrogenism. Moreover, there is a notable absence of an effective in vivo model for pre-clinical testing. In this work, we developed an animal model for CAH with the clinically relevant point mutation p.R484Q in the previously humanized CYP21A2 mouse strain. Mutant mice showed hyperplastic adrenals and exhibited reduced levels of corticosterone and 11-deoxycorticosterone and an increase in progesterone. Female mutants presented with higher aldosterone concentrations, but blood pressure remained similar between wildtype and mutant mice in both sexes. Male mutant mice have normal fertility with a typical testicular appearance, whereas female mutants are infertile, exhibit an abnormal ovarian structure, and remain in a consistent diestrus phase. Conclusively, we show that the animal model has the potential to contribute to testing new treatment options and to prevent comorbidities that result from hormone-related derangements and treatment-related side effects in CAH patients.

Harvard-Zitierstil: Thirumalasetty, S., Schubert, T., Naumann, R., Reichardt, I., Rohm, M., Landgraf, D., et al. (2024) A Humanized and Viable Animal Model for Congenital Adrenal Hyperplasia-CYP21A2-R484Q Mutant Mouse, International Journal of Molecular Sciences, 25(10), Article 5062. https://doi.org/10.3390/ijms25105062

APA-Zitierstil: Thirumalasetty, S., Schubert, T., Naumann, R., Reichardt, I., Rohm, M., Landgraf, D., Gembardt, F., Peitzsch, M., Hartmann, M., Sarov, M., Wudy, S., Reisch, N., Huebner, A., & Koehler, K. (2024). A Humanized and Viable Animal Model for Congenital Adrenal Hyperplasia-CYP21A2-R484Q Mutant Mouse. International Journal of Molecular Sciences. 25(10), Article 5062. https://doi.org/10.3390/ijms25105062