New Autism Mouse Models Highlight Gene Dosage Effects

Two new genetic mouse models that debuted this week show that having too many or too few copies of certain genetic regions leads to an array of symptoms reminiscent of autism.A study published yesterday in Science Translational Medicine found that mice carrying three copies of the autism candidate gene UBE3A have repetitive grooming behaviors, fewer vocalizations and little interest in social interactions. UBE3A is located in chromosomal region 15q11-13, the most common place in the genome for genetic causes of autism.This came on the heels of another report, published 3 October in the Proceedings of the National Academy of Sciences, on another much-talked-about region, 16p11.2. The researchers showed that mice carrying only one copy of this region have severe repetitive behaviors, larger-than-normal volumes of many brain regions and tend to die young. By contrast, those with three copies have low motor activity, smaller-than-normal volumes of the same brain areas and are relatively healthy. These data were first presented at a Boston symposium in December.Deletions of this segment, informally known as 16p, crop up in roughly one percent of individuals with autism. Duplications also show up in a few people with autism and, more commonly, in people with schizophrenia.Both papers highlight what is sometimes called the 'Goldilocks phenomenon' of gene dosage, notes Jeremy Veenstra-VanderWeele, assistant professor of psychiatry, pediatrics and pharmacology at Vanderbilt University in Nashville, Tennessee, who was not involved in either study. "You can have too little and end up with a problem in brain development or synaptic function, or you can have too much and end up with same sort of problem."The new mice are useful because "we don't know where the boundaries of these 'genetic disorders' really are," he says.Read more at...SFARI, October, 2011.