B6.129P2-Hrh1^tm1Wtn/BrenJ

Stock number: 029346
Product name: H1R KO
Research areas: Immunology, Inflammation and Autoimmunity Research, Neurobiology Research

Description

Histamine receptor H1 (H1R) KO mice may be useful when studying the role of histamine during allergic reaction and the regulation of neurotransmission.

Detailed description

H1R KO mice have a neo cassette, in reverse orientation to the gene, replacing the initiation codon of the histamine receptor H1 (Hrh1) gene, abolishing gene expression. Homozygotes are viable and fertile. H1R is a G protein-coupled receptor that mediates the contraction of smooth muscles and neurotransmission in the central nervous system. It is involved in multiple processes including memory and learning, circadian rhythm, and thermoregulation. It is also known to contribute to inflammatory responses and allergic reactions. H1R KO mice have increased amounts of brown and white adipose tissue, with increased body weight after 28 weeks of age. At 48 weeks of age mice have decreased circulating insulin levels, with increased leptin, free fatty acid, and triglyceride levels. These mice also display decreased T and B cell proliferation, and decreased levels of some immunoglobulins such as IgM and IgG3 following stimulation with ovalbumin.

Development

A targeting vector was designed to replace the initiation codon of the histamine receptor H1 (Hrh1) gene with a neomycin resistance (neo) cassette in reverse orientation to the gene. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6 females. Offspring were bred to C57BL/6J mice for at least 20 generations. 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 (Stock No. 000664).

Allele

Symbol: Hrh1^tm1Wtn
Name: targeted mutation 1, Takeshi Watanabe
MGI accession ID: MGI:2182945
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Hrh1
Marker name: histamine receptor H1
Chromosome: 6
Strain of origin: 129P2/OlaHsd
Molecular note: A 0.8 kb fragment containing the initiation codon was replaced with a neomycin selection cassette inserted in reverse transcriptional orientation relative to the gene. Receptor binding studies on brain sections of homozygous mice confirmed that no functional protein was made from this allele.