FVB/N-Tg(GFAP-Cadm1/EGFP)42Oje/J

Stock number: 018548
Research areas: Neurobiology Research, Reproductive Biology Research, Research Tools

Description

This GFAP-DNSynCAM1 transgenic line expresses a dominant-negative form of the CADM1 protein that lacks the intracellular domain, exhibits hyperactivity, increased aggression, and has applications in studies of attention-deficit hyperactive disorder (ADHD).

Detailed description

GFAP-DNSynCAM1 transgenic mice express a dominant-negative form of the CADM1 protein that lacks the intracellular domain in an astrocyte-specific fashion, under the control of the human GFAP, glial fibrillary acidic protein, promoter. The transgene is expressed in the brain, and the expression pattern of the transgene mimics the endogenous gene expression pattern, as determined by immunohistochemical and Western blot analysis of EGFP. Transgenic mice on the FVB background display hyperactivity increased spontaneous locomoter activity in the open field, reduced anxiety in the zero maze, altered response to d,l-amphetamine and increased aggression. Behavioral tests reveal that transgenic mice, on the mixed B6;FVB background, have a disrupted diurnal pattern with increased total activity and reduced resting times during the light phase. Mice hemizygous for the transgenic insert are viable and fertile, although female transgenic mice have delayed puberty onset (by approximately 6 days), disrupted estrous cycles, and reduced fecundity (transgenic litter size approximately 65% of wildtype control litter size). The Donating Investigator reports that the strain cannot be maintained as homozygotes. There is no difference between the phenotype exhibited by homozygotes compared to hemizygotes.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A transgenic construct containing a mutant mouse Cadm1 (cell adhesion molecule 1) sequence encoding a dominant-negative form of the protein that lacks the intracellular domain (EGFP replaced the sequence encoding the intracellular domain), under the control of the human GFAP, glial fibrillary acidic protein, promoter, was injected into fertilized FVB/NJ mouse eggs. Founder line 42 was subsequently established. The mice were maintained the FVB/N background by the Donating Investigator. Upon arrival at The Jackson Laboratory, the mice were crossed to FVB/NJ (Stock No. 001800) at least once to establish the colony.

Allele

Symbol: Tg(GFAP-Cadm1/EGFP)42Oje
Name: Transgene insertion 42, Sergio R Ojeda
MGI accession ID: MGI:5435596
Generation method: Transgenic
Attributes: Reporter; Dominant negative; Inserted expressed sequence
Marker symbol: Tg(GFAP-Cadm1/EGFP)42Oje
Marker name: Transgene insertion 42, Sergio R Ojeda
Chromosome: UN
Strain of origin: FVB/NJ
Expressed genes: Cadm1,cell adhesion molecule 1,mouse, laboratory; GFP,Green Fluorescent Protein,
Site of expression: A dominant-negative form of the CADM1 and GFP are expressed in the brain.
Molecular note: Mouse Cadm1 sequence encoding a dominant-negative form of the protein lacking the intracellular domain (EGFP replaced the sequence encoding the intracellular domain) was placed under the control of the human GFAP promoter.