B6.129-Dlgap3^tm1Gfng/J

Stock number: 008733
Research areas: Neurobiology Research, Research Tools

Description

Sapap3^-/- (SAPAP3-null) mice exhibit characteristics of human obsessive compulsive disorder (excessive self-grooming, facial lesions, anxiety behavior and therapeutic response to fluoxetine) and altered cortico-striatal neurotransmission. These mice may be useful in studying OCD and other neuropsychiatric disease.

Detailed description

The Sapap3^- (SAPAP3-null) allele has a deletion of the exon containing the translation initiation codon. No full-length protein expression from the targeted allele is detected by western blot analysis of brain lysate and postsynaptic density fraction. Heterozygous mice (Sapap3^+/-) are viable and fertile with no reported abnormalities. Occasionally, heterozygotes older than ten months of age may have facial skin lesions. Homozygous mice (Sapap3^-/-) exhibit behavioral and neurological abnormalities. Specifically, Sapap3^-/- mice have characteristics of human obsessive compulsive disorder (excessive self-grooming, facial lesions and anxiety behavior) and altered cortico-striatal neurotransmission. The obsessive compulsive disorder behaviors of homozygous mice can be ameliorated by fluoxetine treatment. Homozygotes are fertile and breed when young and devoid of skin lesions. However, the donating investigator does not recommend maintaining the colony by breeding homozygous mice together: this would select mice for less severe phenotypes as they will breed better than the severe mice. The donating investigator also reports they have not observed Sapap3^-/- mice excessively grooming their cagemates.

Development

A targeting vector was designed designed by Dr. Guoping Feng (while at Duke University) to insert a neomycin cassette and delete exon 3 (containing the translation initiation codon) of the synapse-associated protein 90/postsynaptic density protein 95-associated protein 3 locus (Dlgap3; Sapap3). The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. Chimeric mice were bred with C57BL/6 mice to establish the mutant colony. The donating investigator reports that Sapap3^- mice were subsequently backcrossed to C57BL/6J mice for at least ten generations. During backcrossing, the Y chromosome was fixed to the C57BL/6J genetic background. In 2014, Dr. Feng (now at Massachusetts Institute of Technology) sent heterozygous mice to The Jackson Laboratory Repository. Upon arrival, males were used to cryopreserve sperm. To establish the living mouse colony, an aliquot of the frozen sperm was used to fertilize oocytes from C57BL/6J inbred females (Stock No. 000664).

Allele

Symbol: Dlgap3^tm1Gfng
Name: targeted mutation 1, Guoping Feng
MGI accession ID: MGI:3759300
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Dlgap3
Marker name: DLG associated protein 3
Chromosome: 4
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: Exon 3 containing the translation initiation codon was replaced with a neo cassette. The absence of protein product was confirmed by western blot analysis of brain lysate and postsynaptic density fraction.