Knockout Mice In Cushing’s Syndrome Research

New Insight on the Effects of the ARMC5 Gene on Patients Suffering from Cushing’s Syndrome

Genetic experiments and knockout mice have recently helped scientists at the University of Montreal Hospital Research Centre (CRCHUM) gain new insight on the effects that eliminating a specific gene known as ARMC5 can have in inducing particular ailments and predispositions to disease.

After invalidating mice through a series of experiments through genetic knockout, they have found the gene to cause symptoms similar to that of a rare disorder named Cushing’s syndrome.

The ARMC5 Gene and Its Effect on Knockout Mice

Until recently, the role of the ARMC5 gene was unknown. After researchers at CRCHUM successfully removed it in knockout mice, they noticed most of the mice had died prior to their development and the surviving specimens displayed symptoms consistent to a completely new syndrome temporarily named the Armadillo syndrome.

Without the gene, the mice developed impaired immune, cardiovascular and nervous systems. Also, it has been observed that, when they grow older, the mice suffer from abnormally enlarged endocrine glands and high blood cortisol levels – symptoms consistent with a specific type of Cushing’s syndrome known as bilateral macronodular adrenal hyperplasia, a rare disorder causing similar developmental faults in human patients.

According to CRCHUM researcher, Jiangping Wu, 30 genes were selected for the study out of the approximately 30,000 that make up the mouse’s genome, and ARMC5 proved to show the most promising and unique results.

ARMC5 Mutations and Cushing’s Syndrome

The aforementioned variety of Cushing’s syndrome affects less than 1% of the human population of the planet, and normally results in patients developing benign tumors on the exterior of the adrenal glands. The syndrome was identified as a genetically transmitted disorder, and results in the glands developing excess cortisol, often leading to the development of serious disorders like depression, HBP, diabetes or cardiovascular disease. Treatments include a few medical drugs and surgical ablation procedures.

According to the studies of Cushing’s syndrome expert, André Lacroix, half the patients affected by adrenal hyperplasia are carriers of ARMC5 mutations. Unlike in past findings, dr. Wu’s research bridges the gap to show that the impact of this gene and the disorder itself may often have an effect not only on the adrenal glands, but on the immune system and several other key systems of the body as well.

Mice affected by ARMC5 mutations have had unforeseen developmental problems, being smaller, developing bent tails, and showing signs of hypertension. These problems are consistent with spinal cord issues in human patients suffering from spina bifida.

Future Studies

Dr. Wu’s research shows promise for future studies of the link between ARMC5, the Armadillo syndrome and several serious diseases that include Cushing’s syndrome as well as other diseases caused by mutations of the gene in humans.

The next step in this research will be to set up clinical studies in order to observe patients affected by the mutation. Key goals include the early detection of bilateral macronodular hyperplasia, as well as immune, cardiovascular and neurological problems. Moreover, the experts at CRCHUM also hope that the new mouse model will help them gain new insights regarding which specific molecules the ARMC5 gene interacts with, and how a better treatment might be devised for patients suffering from bilateral hyperplasia.

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