B6N;129-Prkg2^tm1Pfe/J

Stock number: 028500
Product name: cGKII^-
Research areas: Developmental Biology Research, Endocrine Deficiency Research, Internal/Organ Research, Neurobiology Research

Description

Homozygous cGKII (Prkg2) knockout mice exhibit dwarfism, resistance to E. coli infection, anxiety-like behavior and elevated alcohol consumption. These mice may be useful in studying the role of cGMP protein kinases in a variety of physiological processes.

Detailed description

cGKII (PRKG2 or protein kinase, cGMP-dependent, type II) mediates cellular signaling induced by nitric oxide and cGMP. Expression of cGKII is concentrated in the brain, lung and intestinal mucosa. Depending on the tissue, cGKII is implicated in behavioral responses, the regulation of fluid balance in the intestine and in endochondral ossification at the growth plates. The cGKII knockout allele has a neo cassette replacing part of exon 2 of the Prkg2 gene. Homozygous mice exhibit dwarfism, short limbs, cranial abnormalities, resistance to E. coli infection, anxiety-like behavior but, not aggressive behavior, and elevated alcohol consumption. These mice may be useful in studying the role of cGMP protein kinases in a variety of physiological processes.

Development

A targeting vector was designed in the laboratory of Dr. Reinhard Fässler (Technische Universität München) to replace a portion of the second coding exon (nucleotides 903 to 1070) and the following intron. The second exon encodes the first part of the cGMP binding pocket. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to a 129 substrain. Mice from the colony were transferred to the laboratory of Dr. Edward Ziff (New York University Medical Center). Subsequently the mice were crossed to C57BL/6NTac for at least one generation. Upon arrival, mice were bred to C57BL/6NJ for 1 generation to establish the colony.

Allele

Symbol: Prkg2^tm1Pfe
Name: targeted mutation 1, Alexander Pfeifer
MGI accession ID: MGI:2449704
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Prkg2
Marker name: protein kinase, cGMP-dependent, type II
Chromosome: 5
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A 308 bp fragment of the second coding exon was replaced with a neomycin selection cassette inserted by homologous recombination. The disrupted exon encoded a portion of the cGMP binding pocket. Northern blot, RT-PCR, and Western blot analyses indicated an absence of normal transcript and protein in homozygous mutant mice. Functional ablation was confirmed by a lack of cGMP-stimulated phosphotransferase activity in jejunal homogenates.