Shattering a long-held scientific assumption, Israeli researchers have discovered that a gene once thought to only help build the brain before birth continues to play a critical role throughout adult life.

Weizmann Institute of Science researchers showed that suppressing the Orthopedia (Otp) gene in adult male mice severely impaired their ability to cope with stress, while also disrupting their thyroid function and metabolic balance.

“Otp does not stand for one-time password,” Dr. Yael Kuperman of the Weizmann Institute of Science quipped to The Times of Israel in a joint Zoom conference call with collaborator Prof. Gil Levkowitz.

Switching off Otp in adult mice did not simply alter a single hormone, the researchers said. Rather, it triggered widespread disruptions to the mice’s emotional and physical health.

The study, published in Endocrinology, details how the team used sophisticated genetic tools to selectively turn off the mice’s Otp, causing a spike in their cholesterol levels, blood sugar and overall metabolism, and also giving them a feeling of depression and a sense of helplessness.

“The Otp gene is a multitasker that regulates physiological daily life activities that are important for our well-being,” Levkowitz said. “The gene is related to survival responses, including eating, drinking, social behaviors, reproduction and coping with stress.”

The findings could pave the way for more precise treatments that target individual symptoms of anxiety, stress and metabolic disorders.

The challenge of understanding the Otp gene

While it is known that Otp helps build the embryonic brain, its function in fully grown mammals has not been explored simply because mice born without the Otp gene cannot survive past infancy. That meant researchers lacked a way to study how the gene operates in adulthood.

About 70% of human genes are found in zebrafish, so about a decade ago, Levkowitz researched the Otp gene in these small freshwater minnows.

Since zebrafish carry two versions of the Otp gene with overlapping functions, the fish can survive when one........

© The Times of Israel