B6N.129P2-Adora1^tm1Bbf/J

Stock number: 014161
Product name: A₁R knock-out (A1R KO)
Research areas: Cardiovascular Research, Developmental Biology Research, Diabetes and Obesity Research, Neurobiology Research

Description

A₁R knock-out has a neomycin resistance cassette replacing exon 2 of the endogenous adenosine A1 receptor gene. These mice may be useful for studying pharmacological uses of adenosine regarding cardiac function, oxygen consumption, and insulin secretion.

Detailed description

In this A₁R strain, neomycin resistance (neo) cassette replaces exon 2 of the endogenous adenosine A1 receptor (Adora1) gene, abolishing gene function. Heterozygotes are viable, fertile, and normal in size. Homozygotes have a decreased survival rate after 5 months of age and males exhibit reduced fertility. The binding of adenosine to A₁R inhibits excitatory synaptic transmissions in the brain and causes dilation of veins and arteries. These mice exhibit an increase in hyperalgesia, anxiety, hypoxic damage, lipolysis, insulin secretion, osteopetrosis, and susceptibility to epilepsy. They also have abolished tubuloglomerular feedback and a reduction in ischemic preconditioning. These mice have a decrease recovery rate after hypoxic or ischemic stress.

Development

A targeting vector was designed to replace exon 2 of the adenosine A1 receptor (Adora1 or A₁R) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129P2/OlaHsd-derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6N females to generate a colony of A₁R mice. These mice were backcrossed on to a C57BL/6NTac background using a speed congenic protocol at The Jackson Laboratory. Mice were bred to C57BL/6NJ (Stock No. 005304) for at least one generation to establish the colony.

Allele

Symbol: Adora1^tm1Bbf
Name: targeted mutation 1, Bertil B Fredholm
MGI accession ID: MGI:2180136
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Adora1
Marker name: adenosine A1 receptor
Chromosome: 1
Strain of origin: 129P2/OlaHsd
Molecular note: A PGK-neo cassette replaced most of the coding region and a portion of the of the 3' flanking region of the targeted exon. An absence of the normal protein was observed using in situ hybridization and autoradiographic analysis using a labeled ligand, DPCPX.