Maternal genetics could contribute to autism-like traits in mice through irritation | Spectrum
Protective function: PTEN pups from wild-type mice (left) have more neurons (brown) than those from PTEN mothers (right).
Women who are genetically predisposed to inflammation may be more likely to have children with characteristics of autism, according to a new study in mice.
Previous work suggests that inflammation in a pregnant woman – due to a severe infection or an autoimmune disease, for example – is linked to a slightly increased chance of autism in her child. The new study examined the role a woman’s genes might play in such inflammation and the development of the fetal brain.
“Our results suggest that maternal genetics alone may be a contributing factor in increasing the risk of autism spectrum disorder in children,” said lead researcher Charis Eng, chair of the Cleveland Clinic’s Genomic Medicine Institute, Ohio . “These mothers would have genes that predispose them to increased inflammation only in response to the pregnancy itself and not as a result of drugs, toxins or infections.”
Scientists focused on PTEN, a gene that encodes a tumor-suppressing protein that also helps make neuronal connections. PTEN mutations account for up to 2 percent of all autism cases and 17 percent of cases where the child has an unusually large head.
Eng and her colleagues developed mice with only one fully functional copy of PTEN instead of the usual two. They crossed these mice with wild-type mice, resulting in some pups that had two fully functional PTEN genes and others that only had one.
In the first eight days after birth, more pups from female PTEN mice bred with wild-type males died than those from wild-type females bred with PTEN males. And the pups from these PTEN mothers tended to have unusually large heads and behaviors reminiscent of autism, such as repetitive activities and decreased socializing with unfamiliar mice, even when they had two fully functional PTEN genes.
In addition, puppies with only one functional PTEN gene and a wild-type mother had less pronounced autism-like behaviors, suggesting that maternal genetics may also play a protective role against genetic predisposition, the researchers say.
Interacting genes:
Nonetheless, of all puppies born to model PTEN mice, those with only one functional copy of PTEN had more severe autism-like behaviors than their wild-type littermates, underscoring the influence of the puppy’s genes.
“We know that in genes linked to autism like PTEN or FMRP, there can be people with the same mutation in a gene, but only 20 to 50 percent of them will end up with autism, so there is either a gene-gene interaction or gene- Environmental interaction is taking place, ”says Bryan Luikart, Associate Professor of Molecular and Systems Biology at Dartmouth University in Hanover, New Hampshire, who was not involved in the study. “These new findings indicate both: a gene-environment interaction with a kind of inflammation and a gene-gene interaction between mothers and offspring.”
Compared to wild-type female mice, PTEN female mice had significantly lower levels of the anti-inflammatory molecule IL-10 during pregnancy and their fetuses had correspondingly lower levels of important immune proteins in their liver. In addition, according to post-mortem tissue analyzes, these fetuses showed signs of neuron loss and less barrier to protecting the brain from toxins and invaders. The pups also had less mature neuron-supporting glial cells. The results were published in June. released Translational Psychiatry.
Future work should test other genes for their ability to trigger inflammation during pregnancy, says Eng. Researchers should also determine exactly how the disruption of IL-10 activity can affect brain cells, says Jaclyn Schwarz, an adjunct professor of psychology and brain sciences at the University of Delaware at Newark, Delaware, who did not participate in the study.
Scientists could one day predict inflammation during pregnancy from a woman’s genes, says Schwarz. Clinicians could then potentially treat such inflammation with compounds that enhance IL-10, adds Eng.
Quote this article: https://doi.org/10.53053/EXRK3922
