Exon 4 of the mouse Celf6 gene has been excised in this targeted knock-out strain which may be useful as a model of autism.
Nathaniel Heintz, The Rockefeller University
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.
A targeting vector containing loxP sites flanking exon 4 and an FRT-flanked neomycin-resistance cassette was electroporated into B6(Cg)-Tyrc-2J/J-derived ES cells. Resultant chimeric mice were bred to germline Flpe-expressing C57BL/6 background mice to excise the neomycin selection cassette. These mice were maintained on a C57BL/6 genetic background by the donating lab. Exon 4 was excised through crosses with an actin-cre mouse. The Tyrc-2J (albino) allele may still be retained by some of the animals.
|Allele Name||targeted mutation 1.2, Joseph D Dougherty|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Celf6, CUGBP, Elav-like family member 6|
|Strain of Origin||B6(Cg)-Tyrc-2J|
|Molecular Note||LoxP sites were inserted, with an adjacent FRT flanked neomycin resistance cassette, upstream and downstream of exon 4. Mice were subsequently mated to flp expressing mice and the offspring mated to cre expressing mice to delete, first, the selection cassette, and then exon 4. Quantitative RT-PCR from mouse brain confirmed decreased mRNA. Immunological studies confirmed the absence of protein product in the brain.|
Homozygous and heterozygous mice are viable and fertile.
When using the Celf6- mouse strain in a publication, please cite the originating article(s) and include JAX stock #028389 in your Materials and Methods section.