B6.129-Grk2^tm1Mca/J

Stock number: 012430
Research areas: Cardiovascular Research, Developmental Biology Research

Description

This Adrbk1 (adrenergic receptor kinase, beta 1; also known as Grk2) targeted mutation strain may be useful for delineating the role of GRK2 activity in developmental processes. Homozygotes show defects which include failure of the heart to develop properly (thin myocardium syndrome) leading to embryonic lethality. Heterozygotes exhibit altered adrenergic receptor-regulated heart function as adults.

Detailed description

Adrbk1 (adrenergic receptor kinase, beta 1; also known as Grk2) is the main G-protein-coupled receptor kinase in developing embryos, and lack of GRK2 expression results in embryonic lethality before gestational day 15.5. Homozygotes with this targeted mutation show defects which include failure of the heart to develop properly (thin myocardium syndrome). This strain will be useful for delineating the role of GRK2 activity in developmental processes. Heterozygotes exhibit altered adrenergic receptor-regulated heart function when tested as adults, and these mice can be useful for exploring the role of GRK2 function in the regulation of any G-protein coupled receptor subtype. Homozygous embryos lack GRK2 immunoreactivity. Heterozygote mouse brain and heart have 50% of normal GRK2 immunoreactivity.

Development

Exons 5-8 were replaced with a PGK-neomycin resistance cassette (in the anti-sense orientation) using 129-derived embryonic stem (ES) cells. Exon 8 encodes the consensus catalytic subdomain I of the protein kinase. This line was backcrossed to C57BL/6 for more than ten generations by the donating laboratory.

Allele

Symbol: Grk2^tm1Mca
Name: targeted mutation 1, Marc Caron
MGI accession ID: MGI:2180127
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Grk2
Marker name: G protein-coupled receptor kinase 2
Chromosome: 19
Strain of origin: 129
Molecular note: A neomycin cassette replaced exons 5 through 8, encoding catalytic subdomain I that contains a portion of an ATP-binding site. The insertion also altered the downstream reading frame. Northern blot analysis of mutant embryos showed a 62% reduction of transcripts in heterozygotes and an absence of transcripts in homozygotes. Western blot analysis showed correlative results.