In female mammals, the gene on one copy of the X chromosome is usually inactive
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A study in mice suggests that female mammals are at a higher risk of developing autoimmune diseases such as lupus because extra copies of genes that should be permanently turned off become reactivated as they age.
says the findings may apply to all mammals, including humans Celine Morey Researchers at Université Paris Cité in France may explain why older women are more likely to develop diseases such as rheumatoid arthritis.
Male mammals usually have one X chromosome and one Y chromosome, while most female mammals have two copies of the X chromosome. If all genes on both X chromosomes are active, women will get a double dose of the gene product compared to men.
Instead, soon after an embryo begins to develop, most genes on one of the two copies of the X chromosome are turned off, a phenomenon called X inactivation.
Morey and her colleagues set out to study this process by breeding mice lacking a gene involved in X inactivation. This deletion doesn’t completely prevent X from inactivating — which would be fatal — but it does weaken its strength.
At first, the mice behaved normally. “We have to wait until the mice get older before we can finally detect the problem, because otherwise they’ll be happy,” Morey said.
In old age, the mice developed lupus-like symptoms, such as enlarged spleens.
The team found that as the mice aged, several key genes on the inactive X chromosome were reactivated in immune cells.These genes regulate the immune system, and one of them is called TLR7known to affect a person’s risk of developing lupus.
It is suspected that higher doses of genes, e.g. TLR7 People with two X chromosomes are more resistant to many infectious diseases, but also more susceptible to autoimmune diseases. The new study provides the strongest evidence to date that higher doses may occur due to a failure to maintain X inactivation.
Morey hopes the findings will lead to better treatments for autoimmune diseases such as rheumatoid arthritis, which is more common in older adults and women than men.
“If we identify the genes involved, we might be able to design some treatments that target specific key factors,” Morey said.
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