Mice with a defected human gene answerable for a rare genetic disease, called congenital adrenal hyperplasia, have been developed for the primary time. The achievement, presented on the twenty fifth European Congress of Endocrinology, may help to develop recent therapies for individuals with essentially the most common form of congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is a bunch of inherited conditions, which affects about 1 in 15,000 births. In essentially the most common form, called 21-hydroxylase deficiency, mutations within the CYP21A2 gene cause the adrenal glands – a pair of small organs positioned above the kidneys – to provide low levels of cortisol and excess amounts of androgen hormones, equivalent to testosterone. This results in early puberty, girls having male features, and various health issues. Currently steroid hormone substitute therapy is used for treatment, but this will likely often have harmful unwanted effects.

On this study, researchers from the University Hospital Carl Gustav Carus in Dresden, Germany, replaced the gene Cyp21a1 in mice with the human gene CYP21A2 carrying a mutation. They found that the genetically modified mice at 20 weeks had enlarged adrenal glands while expressing the human mutated gene. As well as, similarly to the human disease, the mutation caused each female and male mice to have low levels of corticosterone – the most important stress hormone in mice that’s the corresponding to cortisol in humans – and other hormonal imbalances.

Although animal models for congenital adrenal hyperplasia exist, that is the primary to breed the human condition in mice and capable of survive with none treatments.

Our mice accurately mimic the symptoms seen in human patients. For instance, the feminine mutant mice even have issues with fertility, which we imagine is likely resulting from the hormonal imbalances triggered by congenital adrenal hyperplasia.”

Shamini Ramkumar Thirumalasetty, Lead Writer

This mouse model will now allow the team to review the mechanisms of the disease and to search out essentially the most effective treatments. “Although novel treatments are being developed to attenuate the unwanted effects of steroid hormones, these drugs lack effective in vivo models for pre-clinical testing,” said Ms Thirumalasetty. “Our mouse can function a superb model to check novel drugs and treatment options for patients with congenital adrenal hyperplasia, equivalent to stem cell therapies, and can facilitate the transition from basic research to the clinic.”

Source:

European Society of Endocrinology