B6.129S6-Adra1d^tm1Jabl/PcsJ

Stock number: 036555
Product name: α1d^-
Research areas: Neurobiology Research, Research Tools

Description

α1d^- knock-in/knock-out mice have a lacZ and a neomycin resistance (neo) cassette inserted into exon 1 of the Adra1d gene, abolishing gene expression. These mice may be useful for studying changes in locomotor behavior in response to both environmental and specific drug-induced cues.

Detailed description

α1d^- knock-in/knock-out mice have a β-galactosidase (lacZ) and a neomycin resistance (neo) cassette inserted into exon 1 of the adrenergic receptor, alpha 1d (Adra1d) gene, abolishing gene expression. Adrenergic receptors are targets for norepinephrine and epinephrine and are involved in behaviors such as exploration, arousal and circadian behavior, and the locomotor and rewarding effects of drugs of abuse, such as psychostimulants and opiates. These receptors appear to be critical in mediating the switch from basal locomotor behavior to an activated state in response to both environmental and specific drug-induced cues. This gene is also involved in physiological responses in the cardiovascular and peripheral nervous system.

Immunohistochemical analysis detects lacZ expression in the olfactory bulb, cortex, hippocampus, and dorsal geniculate and ventral posterolateral nuclei of the thalamus. These mice exhibit normal behavior and locomotor activity during the day. However, during the night wheel-running activity is significantly reduced, and they show a reduction in exploratory rearing behavior in a novel cage environment. α1d^- knock-in/knock-out mice show reduced hyperlocomotion after acute amphetamine administration, and show responses similar to WT after cocaine administration.

Homozygous mice are viable and fertile, yet the donating investigator reports that breeding can be slow.

Development

The α1d^- targeting vector was designed by Dr. Julie Blendy (University of Pennsylvania School of Medicine) to insert a β-galactosidase (lacZ) and a neomycin resistance (neo) cassette into exon 1 of the adrenergic receptor, alpha 1d (Adra1d) gene. The construct was electroporated into 129S6/SvEvTac-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric mice were bred to C57BL/6 mice to generate a colony of α1d^-/- knock-in/knock-out mice. Some of these mice were acquired by Dr. Paul C. Simpson (from UCSF and SF VA Medical Center) and mice were backcrossed 10 generations to C57BL/6J mice (Stock No. 000664). Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Adra1d^tm1Jabl
Name: targeted mutation 1, Julie A Blendy
MGI accession ID: MGI:3612161
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Synonyms: alpha1d^-
Marker symbol: Adra1d
Marker name: adrenergic receptor, alpha 1d
Marker synonyms: Adra1; Adra-1; Adra1a; ADRA1R; Adrd1; ALPHA1; alpha1D-AR; DAR; dJ779E11.2; Gpcr8
Chromosome: 2
Strain of origin: 129S6/SvEvTac
Molecular note: A targeting vector containing a lacZ-neomycin resistance gene was inserted into exon 1. RNAse protection assay confirmed ablation of the gene. Immunohistochemical analysis detected beta-gal expression in the olfactory bulb, cortex, hippocampus, and dorsal geniculate and ventral posterolateral nuclei of the thalamus.