Autism-linked variants converge on two molecular patterns in mouse brains
Gene activity across 17 autism mouse models occurs in either of two opposing transcriptomic states, supporting the idea that diverse genetic changes may converge on a few recurring biological patterns.
A large-scale study of autism mouse models has revealed that diverse genetic changes converge on just two opposing transcriptomic states in the prefrontal cortex. Across 17 mouse lines carrying different autism-linked variants, gene activity in this brain region fell into two distinct patterns. In one state, genes involved in neuron-to-neuron communication were less active, while genes regulating DNA and RNA processing were more active.
The reverse pattern was observed in the second group. This work, published in Science, is a significant step towards organizing the over 100 autism-linked genes into biologically meaningful groups that could guide targeted treatments. The findings also support the idea that some genetic diversity associated with autism may converge on a small number of recurring molecular states.
While the primary distinction between the two groups was the direction of gene-expression changes, the two cortical transcriptome groups responded differently to pharmacological interventions that altered autism-like behaviors in past research. The classification of these two groups is not fixed, as some mice switched groups as they matured.
In humans, an analysis of the prefrontal cortex gene activity in 40 autistic people and 17 non-autistic individuals also showed a separation into two groups with broadly opposite gene activity patterns, although the split was not as clear-cut as in the mice. Although the human pattern is relatively weak, it suggests that the mouse findings may capture something relevant to autism in people.
The researchers emphasize that autism is a developmental condition, and the fact that mice carrying the same variant can fall into different groups depending on sex, brain region, or developmental stage does not undermine the findings. Instead, it highlights that autism's biology may shift as the brain develops. The study also has implications for defining and identifying autism subgroups, suggesting that molecular data could provide a complementary approach to brain imaging or other broad measures.
Written by urgent.news from The Transmitter's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
