The name of the gene is Armc5, for Armadillo repeat containing 5. Until now, its function was unknown. After 10 years of research, a team at Université de Montréal's Hospital Research Centre (CRCHUM) has succeeded in deleting this gene in experimental mice and discovered that its loss gives rise to a heretofore unidentified syndrome. This syndrome is provisionally called Armadillo Syndrome.

A study published in the online journal Nature Communications describes the manifestations of this complex syndrome in mice, and opens up new avenues for the understanding, treatment and prevention of a number of diseases.

“We have created the first animal model of a rare disease linked to a problem of the adrenal glands," said Jiangping Wu, a CRCHUM researcher and medical professor at Université de Montréal. "In addition, we have identified the important roles of this gene in the development of mice and in the immune, nervous and cardiovascular systems."

“We discovered that, when we inactivate the Armc5 gene, about half of the mice die during their embryonic development and those who survive are smaller," said Dr. Wu. "Their immune system has been weakened, and their resistance to infections is poor. Furthermore, when they age, their adrenal glands grow abnormally large and their blood cortisone levels are high just like in human Cushing’s syndrome."

A better understanding of the mechanisms by which this gene controls the development of several organs and of the different manifestations of Armadillo Syndrome could help prevent and treat serious disorders such as Cushing’s syndrome and perhaps other diseases caused by ARMC5 mutations.

“A mutation of the ARMC5 gene can manifest itself through at least four diseases,” said Dr. Wu. “We showed this in the mouse, but we do not yet know whether the consequences in humans will be the same.”

The next step: the researchers will pursue clinical studies in patients affected by this mutation, in order to detect early bilateral macronodular hyperplasia of the adrenals, as well as abnormalities of the immune, neurologic and cardiovascular systems. The CRCHUM researchers also want to utilize this unique murine model to study how this rare disease – bilateral macronodular adrenal hyperplasia – develops, and to identify the molecules with which the Armc5 gene interacts and which could potentially be used as targets for future treatments.