Late in the afternoon last Thursday, in a stately wood-paneled room of the New York Academy of Medicine, five researchers for the first time shared notes on a project they had each been tackling for years: creating mice lacking the SHANK3 gene.SHANK3, located on the tip of chromosome 22, is among the most promising candidate genes for autism, and is found in an estimated one percent of individuals with the disorder. It makes a protein that is critical to the smooth workings of the synapse, the junction between neurons.It is also part of a segment that, when deleted, causes Phelan-McDermid syndrome, a disorder characterized by severe intellectual disability, delayed speech and, usually, autism.In December, Joseph Buxbaum published the first description of a SHANK3 mutant mouse. But his results were surprising: the mouse has only mild social impairments and does not show any of the cognitive impairments seen in people with the deletion.During their lively discussion, the mouse engineers confirmed what they had individually suspected. The typical strategy for deleting a gene — disrupting the front end of its code — is not sufficient to turn off SHANK3, and could account for Buxbaum's results."They realized that they were all having the same problem," moderator James Pickel, director of the transgenic core facility of the National Institute of Mental Health, told SFARI.org on Friday. "It was a big breakthrough."Read more at...SFARI, March 2011.