Dysfunction of the serotonergic system is suspected in several neuropsychiatric diseases, including obsessive compulsive disorder and autism. Human data suggested polymorphisms in CUGBP Elav-like family member 6 (CELF6), an RNA binding protein expressed by serotonergic cells, may contribute to autism risk.
In this targeted mutant strain, exon 4 of Celf6 has been excised in the germline to introduce a premature stop codon in all known isoforms of the mouse gene. As in the human mutation, this is predicted to result in a nonsense-mediated decay of mRNA.
Quantitative RT-PCR from mouse brain confirms a decrease of Celf6 mRNA. Immunofluorescence confirms a loss of signal from cells in all regions of the brain, including raphe neurons. Germline knockout animals have deficits in autism-related behaviors including pup ultrasonic vocalization, alterations of brain serotonin levels, and alterations in reward processing (conditioned place preference). Otherwise, mice appear largely healthy, viable, and fertile with normal performance on many tasks.
