Overview

Also Known As:H1R KO

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

Donating Investigator

Benjamin Renquist, University of Arizona

Genetic overview

Genetic Background	Generation

Hrh1^tm1Wtn

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Hrh1	histamine receptor H1

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

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).

Control Suggestions

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Inoue I; Yanai K; Kitamura D; Taniuchi I; Kobayashi T; Niimura K ; Watanabe T ; Watanabe T. 1996. Impaired locomotor activity and exploratory behavior in mice lacking histamine H1 receptors. Proc Natl Acad Sci U S A 93(23):13316-20PubMed: 8917588 MGI: J:36556

View All References

Genetics

Hrh1^tm1Wtn

Allele Symbol: Hrh1^tm1Wtn

Allele Name	targeted mutation 1, Takeshi Watanabe
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	H1KO; H1R-; H1RKO; Hrh1-; Hrh1^tm1Wat
Gene Symbol and Name	Hrh1, histamine receptor H1
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	6
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.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B and T cell deficiency
- Autoimmunity
- Inflammation
Neurobiology Research
- Receptor Defects
  - G protein-coupled receptor

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Hrh1^tm1Wtn/Hrh1^tm1Wtn
involves: 129P2/OlaHsd * C57BL/6

hematopoietic system phenotype

decreased T cell number
- the number of CD5+ B220+ T cells is slightly decreased (21.0+/-8.6% compared to 39.5+/-9.1% in wild-type mice)

decreased IgM level
- following stimulation with TNP-Ficoll, anti-TNP IgM antibodies are 9-fold lower than in similarly treated wild-type mice
- following challenge with ovalbumin, anti-ovalbumin IgM antibodies are lower than in similarly treated wild-type mice

decreased T cell proliferation
- Normal - however, T cell proliferation in response to PHA is normal
- T cell proliferation in response to ovalbmin is reduced 4- to 6-fold compared to in wild-type mice
- T cell proliferation in response to anti-CD3-epsilon is reduced 5- to 8-fold compared to in wild-type mice

decreased B cell proliferation
- Normal - however, B cell proliferation in response to IL-4 alone or in combination with CD40LG or LPS is normal
- B cell proliferation in response to anti-IgM is reduced 3- to 4-fold compared to in wild-type mice

decreased IgG3 level
- IgG3 levels are slightly lower than in wild-type mice
- following challenge with ovalbumin, anti-ovalbumin IgG3 antibodies are lower than in similarly treated wild-type mice

behavior/neurological phenotype

abnormal locomotor circadian rhythm
- Normal - however, total ambulation during a 24 hours period is normal
- the ratio of ambulation during the light phase to total ambulation during 24 hours is increased compared to in wild-type mice
- mice exhibit increased locomotor activity during early portions of the light phase and decreased ambulation during the dark phase of a 12 hours light 12 hour dark cycle relative to similarly treated wild-type mice

decreased vertical activity
- mice rear less when placed in a new environment compared to wild-type mice

abnormal behavior
- during passive avoidance testing, mice display more frequent urination and defecation and decreased movement compared to wild-type mice
- Normal - however, passive avoidance behavior is normal

decreased exploration in new environment
- despite normal motor coordination, mice exhibit decreased ambulation and time of rearing for the first 30 minutes when placed in a new environment

immune system phenotype

decreased interleukin-2 secretion
- following in vitro stimulation with ovalbumin or anti-CD3 epsilon antibodies, cells produce less IL-2

decreased IgG3 level
- following challenge with ovalbumin, anti-ovalbumin IgG3 antibodies are lower than in similarly treated wild-type mice
- IgG3 levels are slightly lower than in wild-type mice

decreased B cell proliferation
- Normal - however, B cell proliferation in response to IL-4 alone or in combination with CD40LG or LPS is normal
- B cell proliferation in response to anti-IgM is reduced 3- to 4-fold compared to in wild-type mice

decreased T cell number
- the number of CD5+ B220+ T cells is slightly decreased (21.0+/-8.6% compared to 39.5+/-9.1% in wild-type mice)

decreased interferon-gamma secretion
- following in vitro stimulation with ovalbumin or anti-CD3 epsilon antibodies, cells produce less interferon-gamma than wild-type mice

decreased T cell proliferation
- T cell proliferation in response to ovalbmin is reduced 4- to 6-fold compared to in wild-type mice
- T cell proliferation in response to anti-CD3-epsilon is reduced 5- to 8-fold compared to in wild-type mice
- Normal - however, T cell proliferation in response to PHA is normal

decreased IgM level
- following challenge with ovalbumin, anti-ovalbumin IgM antibodies are lower than in similarly treated wild-type mice
- following stimulation with TNP-Ficoll, anti-TNP IgM antibodies are 9-fold lower than in similarly treated wild-type mice

increased interleukin-4 secretion
- following in vitro stimulation with ovalbumin or anti-CD3 epsilon antibodies, cells produce more IL-4 than wild-type mice

cellular phenotype

decreased B cell proliferation
- B cell proliferation in response to anti-IgM is reduced 3- to 4-fold compared to in wild-type mice
- Normal - however, B cell proliferation in response to IL-4 alone or in combination with CD40LG or LPS is normal

decreased T cell proliferation
- Normal - however, T cell proliferation in response to PHA is normal
- T cell proliferation in response to ovalbmin is reduced 4- to 6-fold compared to in wild-type mice
- T cell proliferation in response to anti-CD3-epsilon is reduced 5- to 8-fold compared to in wild-type mice

The following phenotype relates to a compound genotype created using this strain

Genotype: Hrh1^tm1Wtn/Hrh1^tm1Wtn
B6.129P2-Hrh1

behavior/neurological phenotype

increased food intake
- Normal - however, at 12 weeks of age food consumption is normal
- at 48 weeks of age, mice consume slightly more food than wild-type mice

decreased food intake
- unlike in wild-type mice, intraperitoneal administration of the histamine agonist methyl(2[2-pyridyl]ethyl)amine dyhydrochloride (1 ug/g for 7 days) results in decreased food intake
- Normal - however, intracerebroventricular administration of methyl(2[2-pyridyl]ethyl)amine dyhydrochloride has no effect on mice

abnormal circadian feeding behavior
- at 48 weeks, the ratio of food consumed in the light versus dark phase is smaller than in wild-type mice

growth/size/body region phenotype

decreased body weight
- unlike in wild-type mice, intraperitoneal administration of the histamine agonist methyl(2[2-pyridyl]ethyl)amine dyhydrochloride (1 ug/g for 7 days) results in decreased body mass
- Normal - however, intracerebroventricular administration of methyl(2[2-pyridyl]ethyl)amine dyhydrochloride has no effect on mice
- during 4 week on a feeding schedule, mice fail to gain weight as do wild-type mice despite equivalent food consumption

increased body weight
- after 28 weeks of age mice exhibit increased body mass relative to wild-type mice

hematopoietic system phenotype

increased IgG level
- following ovalbumin challenge, IgG1, IgG2a and IgG2b levels are increased relative to similarly treated wild-type mice

increased IgM level
- following ovalbumin challenge, IgM levels are increased relative to similarly treated wild-type mice

homeostasis/metabolism phenotype

abnormal response/metabolism to endogenous compounds
- following intracerebroventricular administration of 0.5 ug leptin or intraperitoneal injection of 50 ug of leptin, mice exhibit a smaller decrease in food consumption and body mass relative to wild-type

decreased circulating insulin level
- Normal - however, at 12 weeks of age serum insulin levels are normal
- at 48 weeks of age, serum insulin levels are increased relative to in wild-type mice

increased circulating leptin level
- Normal - however, at 12 weeks of age leptin levels are normal
- at 48 weeks of age, leptin levels are increased by 66% compared to in wild-type mice

increased liver triglyceride level
- mice exhibit 45% more triglycerides in the liver compared to wild-type mice

increased circulating free fatty acids level
- at 48 weeks of age, free fatty acid levels are increased relative to in wild-type mice
- Normal - however, at 12 weeks of age free fatty acid levels are normal

increased triglyceride level
- mice exhibit 20% more triglycerides in skeletal muscle compared to wild-type mice

immune system phenotype

decreased interferon-gamma secretion
- antigen stimulation of splenocytes results in the production of less interferon-gamma compared to in similarly treated wild-type mice

increased IgM level
- following ovalbumin challenge, IgM levels are increased relative to similarly treated wild-type mice

decreased interleukin-13 secretion
- antigen stimulation of splenocytes results in the production of less IL-13 compared to in similarly treated wild-type mice

decreased interleukin-5 secretion
- antigen stimulation of splenocytes results in the production of less IL-5 compared to in similarly treated wild-type mice

decreased inflammatory response
- following challenge with ovalbumin, mice fail to develop lung inflammation as do wild-type mice with fewer eosinophils and lymphocytes detected in the bronchoalveolar lavage
- Normal - however, mice exhibit normal B cell immune responses and inhalation of IL-4 or IL-13 induces lung inflammation

increased IgG level
- following ovalbumin challenge, IgG1, IgG2a and IgG2b levels are increased relative to similarly treated wild-type mice

liver/biliary system phenotype

increased liver triglyceride level
- mice exhibit 45% more triglycerides in the liver compared to wild-type mice

adipose tissue phenotype

increased brown adipose tissue amount
- the amount of brown adipose tissue at 48 weeks of age is increased relative to in wild-type mice
- insulin levels during a 4 week feeding schedule are lower than in mice fed ad libitum
- Normal - however, the levels of brown adipose tissue at 12 weeks of age is normal

increased white adipose tissue amount
- at 28 weeks of age, white adipose tissue is increased by 23%, 48% and 40% in the epididymmal, mesenteric and retroperitoneal fat pads, respectively, compared to wild-type mice

decreased total body fat amount
- unlike in wild-type mice, intraperitoneal administration of the histamine agonist methyl(2[2-pyridyl]ethyl)amine dyhydrochloride (1 ug/g for 7 days) results in decreased in adiposity

increased fat cell size
- adipocytes in the epididymal white adipose tissue are larger than in wild-type mice at 48 weeks of age
- Normal - however, adipocyte size at 12 weeks of age is normal

References

Inoue I; Yanai K; Kitamura D; Taniuchi I; Kobayashi T; Niimura K ; Watanabe T ; Watanabe T. 1996. Impaired locomotor activity and exploratory behavior in mice lacking histamine H1 receptors. Proc Natl Acad Sci U S A 93(23):13316-20PubMed: 8917588 MGI: J:36556

Additional - Hrh1^tm1Wtn related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Hrh1 Alternate1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the H1R KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #029346 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous for Hrh1<tm1Wtn>

Related Products and Services

Frozen Mouse Embryo	B6.129P2-Hrh1<tm1Wtn>/BrenJ	$2595.00
Frozen Mouse Embryo	B6.129P2-Hrh1<tm1Wtn>/BrenJ	$2595.00
Frozen Mouse Embryo	B6.129P2-Hrh1<tm1Wtn>/BrenJ	$3373.50
Frozen Mouse Embryo	B6.129P2-Hrh1<tm1Wtn>/BrenJ	$3373.50

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:H1R KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Hrh1tm1Wtn

Allele Symbol: Hrh1tm1Wtn

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Hrh1tm1Wtn/Hrh1tm1Wtninvolves: 129P2/OlaHsd * C57BL/6

hematopoietic system phenotype

behavior/neurological phenotype

immune system phenotype

cellular phenotype

Genotype: Hrh1tm1Wtn/Hrh1tm1WtnB6.129P2-Hrh1

behavior/neurological phenotype

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

liver/biliary system phenotype

adipose tissue phenotype

References

Additional - Hrh1tm1Wtn related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Hrh1^tm1Wtn

Allele Symbol: Hrh1^tm1Wtn

Genotype: Hrh1^tm1Wtn/Hrh1^tm1Wtn
involves: 129P2/OlaHsd * C57BL/6

Genotype: Hrh1^tm1Wtn/Hrh1^tm1Wtn
B6.129P2-Hrh1

Additional - Hrh1^tm1Wtn related