Overview

Also Known As: Hcrtr1 null, OX1R TD

A floxed transcription-disrupter (TD) ablates expression of the mouse Hcrtr1 gene in this OX1R TD conditional mutant strain. Cre-mediated excision of the TD restores expression under the direction of the native promoter.

Donating Investigator

Thomas Scammell, Beth Israel Deaconess Medical Center

Genetic overview

Genetic Background	Generation

Hcrtr1^tm1Mmsc

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Hcrtr1	hypocretin (orexin) receptor 1

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Research Applications

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The Hcrtr1 (hypocretin (orexin) receptor 1; also called OX1R) gene plays a role in modulating reward and depression-like behavior. Orexin signaling has been implicated in processes as diverse as sleep-wake transitioning, the control of food intake, and autonomic output.

In this conditional mutant OX1R TD strain, a loxP-flanked transcription-disrupter (TD) cassette was introduced to intron 1 of the mouse Hcrtr1 gene to prevent expression of functional protein. Cre-mediated excision of the TD restores expression under the direction of the native promoter.

The impact of this mutation was first tested electrophysiologically using in vitro patch-clamp recordings of noradrenergic neurons of the locus coeruleus (LC), a type of neuron that expresses only OX1R but not OX2R. Orexin-A ligand depolarizes LC neurons from wildtype mice, but has no effect on LC neurons from homozygous OX1R TD mice. The deficit in LC neurons is fully restored after crossing OX1R TD mice with Zp3-Cre mice, which express Cre recombinase in the female germline.

Behaviorally, OX1R TD mice have a significant reduction in behavioral despair in the forced swim test and tail suspension test, but anxiety-like behavior is normal. These mice have normal wake, non-REM, and REM sleep behavior. Cataplexy (episodes of sudden muscle atonia during active wakefulness) does not occur in these mice. OX1/2R TD progeny from crosses with OX2R TD mice (see Stock No. 027707) have severely fragmented sleep/wake behavior, similar to that seen in prepro-orexin null mice.

OX1R TD mice are useful as OX1R null mice in their native state. More importantly, they can be used to study the effects of focal or global restoration of OX1R signaling, using methods that produce focal or germline expression of Cre recombinase, respectively. Focal OX1R restoration can be used to test whether OX1R signaling in a specific brain region is sufficient to rescue specific behaviors.

Development

A floxed transcription disrupter cassette was inserted into intron 1 (formerly identified as intron 3) via homologous recombination in 129-derived embryonic stem (ES) cells. The TD cassette consists of a mouse En2 splice acceptor site followed by an SV40 enhancer, neomycin resistance gene, and two HSV-TK poly(A) signals (a synthetic poly(A) signal/transcriptional pause signal, and another synthetic poly(A) signal followed by a Myc-associated zinc finger protein-binding site). Resultant founder mice were backcrossed to C57BL/6J mice for more than 15 generations by the donating laboratory.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Scott MM; Marcus JN; Pettersen A; Birnbaum SG; Mochizuki T; Scammell TE; Nestler EJ; Elmquist JK; Lutter M. 2011. Hcrtr1 and 2 signaling differentially regulates depression-like behaviors. Behav Brain Res 222(2):289-94PubMed: 21377495 MGI: J:171751

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Genetics

Hcrtr1^tm1Mmsc

Allele Symbol: Hcrtr1^tm1Mmsc

Allele Name	targeted mutation 1, Michael M Scott
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	targeted mutation 1, Michael M Scott; Hcrtr1^tm1Mmsc
Gene Symbol and Name	Hcrtr1, hypocretin (orexin) receptor 1
Gene Synonym(s)	OX1R; Hctr1
Strain of Origin	129
Chromosome	4
Molecular Note	A floxed transcription disrupter cassette was inserted into intron 3 via homologous recombination. In situ hybridization analysis confirmed the absence of expression in the central nervous system of homozygous mice.

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

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

Genotype: Hcrtr1^tm1Mmsc/Hcrtr1^tm1Mmsc
B6.Cg-Hcrtr1

behavior/neurological phenotype

abnormal depression-related behavior
- immobility is also reduced in a tail suspension test
- significant reduction in time immobile and increase in latency to first bout of immobility in a forced swim test suggesting a decrease in depression like behavior

mammalian phenotype

behavior/neurological phenotype
- Normal - no significant differences in anxiety related behavior or activity in a novel environment are detected

References

Scott MM; Marcus JN; Pettersen A; Birnbaum SG; Mochizuki T; Scammell TE; Nestler EJ; Elmquist JK; Lutter M. 2011. Hcrtr1 and 2 signaling differentially regulates depression-like behaviors. Behav Brain Res 222(2):289-94PubMed: 21377495 MGI: J:171751

Additional - Hcrtr1^tm1Mmsc related

Technical Support

Contact Technical Support

Genotyping Protocols
- MELT: Hcrtr2^tm1Tesc alternate1
- Standard PCR: Hcrtr1^tm1Mmsc
- Genotyping resources and troubleshooting
Breeding Considerations

Homozygotes and heterozygotes are viable and fertile.
- Additional Breeding and Husbandry Support
Citation
When using the Hcrtr1 null mouse strain in a publication, please cite the originating article(s) and include JAX stock #027706 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	Genotype	Price
	Heterozygous or wild-type for Hcrtr1<tm1Mmsc>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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.

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Also Known As: Hcrtr1 null, OX1R TD

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Hcrtr1tm1Mmsc

Allele Symbol: Hcrtr1tm1Mmsc

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Hcrtr1tm1Mmsc/Hcrtr1tm1MmscB6.Cg-Hcrtr1

behavior/neurological phenotype

mammalian phenotype

References

Additional - Hcrtr1tm1Mmsc related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Hcrtr1^tm1Mmsc

Allele Symbol: Hcrtr1^tm1Mmsc

Genotype: Hcrtr1^tm1Mmsc/Hcrtr1^tm1Mmsc
B6.Cg-Hcrtr1

Additional - Hcrtr1^tm1Mmsc related