Nature Journal Club

Mikiko C. Siomi

Keio University School of Medicine, Tokyo, Japan

A biologist praises a mouse model of autism inheritance.

Autism, a neurodevelopmental disorder that affects people’s social abilities, has both genetic and non-genetic causes. Chromosomal abnormalities account for 10–20% of autism cases, with duplication of a long stretch of chromosome 15 being the most common. I was excited to read that a mouse model with a similar chromosomal duplication has been generated (J. Nakatani et al. Cell 137, 1235–1246; 2009). These mice exhibit the inflexible behaviour, social abnormalities and increased anxiety often observed in people with autism. However, whereas the engineered mice inherit the duplication from their fathers, human autism cases caused by such a duplication are usually inherited maternally. Further genomic analysis in the mice should find the reason for this discrepancy.

This model deserves special attention as the chromosomal duplication is stably maintained between generations. Also, genes in the duplicated regions seem to work; that is, the expression levels of genes — including HBII52, which affects the function of serotonin, a molecule that has cognitive roles in mood, memory and learning — are higher in the mice, as would be expected with a gene duplication.

Accumulated evidence shows that variations in gene-copy number, such as the chromosomal duplication in this model, are associated with susceptibility to various human diseases; cancer cells, for example, tend to have high gene-copy numbers. Thus, this mammalian model may help us to understand the molecular basis of autism and to investigate the contribution of gene duplication in other genetic diseases. This should encourage many researchers to produce other model systems for copy-number variation using similar techniques; systems that may clarify the contribution of chromosomal duplication, or even the lack of it, in common diseases such as diabetes.


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