FVB.129S2(B6)-Hmox2^tm1Poss/J

Stock number: 008660
Research areas: Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Metabolism Research, Neurobiology Research, Research Tools

Description

Homozygotes for this Hmox2 (heme oxygenase (decycling) 2) targeted null mutation may be useful in studies of oxidative stress and injury, hyperoxia, iron homeostasis and metabolism, vasodilation regulation, and the physiology of neuroprotection.

Detailed description

Homozygotes have reduced total heme oxygenase activity in brain and testes, diminished inflammatory pain response and are more susceptible to hyperoxia with attenuated hypoxic ventilatory response. Cultured neurons from homozygotes exhibit increased neurotoxicity and cell death. Neuronal and endothelial cell damage due to transient focal ischemia and glutamate induced cytotoxicity is increased. Olfactory epithelial neurons have decreased proliferation of neuronal precursors and increased apoptosis. Mutant pulmonary venous myocardium is hypertrophic. After hyperoxic exposure, total lung iron content increased 3.5 fold in homozygotes compared to wild-type. Homozygotes have a slower overall gastrointestinal transit time than wild-type. Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. Although homozygous male animals exhibit ejaculatory abnormalities, both male and female homozygotes are fertile. No gene product (mRNA or protein) is detected by Northern or Western blot analysis in lung tissue or brain. This mutant mouse strain may be useful in studies of oxidative stress and injury, hyperoxia, iron homeostasis and metabolism, vasodilation regulation, and the physiology of neuroprotection.

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 targeting vector containing a PGK-neo selection cassette was used to disrupt exons 4 and 5. The construct was electroporated into 129S2/SvPas derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting male chimeric animals were crossed to C57BL/6 female mice. Heterozygotes were crossed to generate homozygotes. The mice were then backcrossed to C57BL/6 for an unknown number of generations and then backcrossed to FVB for 10 generations before arriving at The Jackson Laboratory.

Allele

Symbol: Hmox2^tm1Poss
Name: targeted mutation 1, Kenneth D Poss
MGI accession ID: MGI:2388325
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Hmox2
Marker name: heme oxygenase 2
Chromosome: 16
Strain of origin: 129S2/SvPas
Molecular note: Approximately 80% of the coding region was replaced with a neomycin selection cassette inserted by homologous recombination. The deleted region included the putative membrane spanning region. Transcript was undetected in homozygous mutant mice by Northern blot analysis of brain tissue. An assay based on bilirubin production indicated complete functional ablation in homozygous mutant mice.