Overview

Also Known As: Hcrtr2 null, OX2R TD

A floxed transcription-disrupter (TD) ablates expression of the mouse Hcrtr2 gene in this OX2R 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

Hcrtr2^tm1Tesc

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Hcrtr2	hypocretin (orexin) receptor 2

View Genetics

Research Applications

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

The Hcrtr2 (hypocretin (orexin) receptor 2; also called OX2R) gene plays a role in regulating arousal, REM sleep, and depression-like behavior.

In this conditional mutant OX2R TD strain, a loxP-flanked transcription-disrupter (TD) cassette was introduced to intron 1 of the 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 histaminergic neurons of the tuberomammillary nucleus (TMN), a type of neuron that expresses only OX2R but not OX1R. Orexin-A ligand depolarizes TMN neurons from wild type mice but has no effect on TMN neurons from homozygous OX2R TD mice.

Behaviorally, OX2R TD mice had normal amounts of wake, non-REM, and REM sleep, but their wake bouts are short during the dark period. Cataplexy (episodes of sudden muscle atonia during active wakefulness) is rare in these mice. OX2R TD mice have milder sleep/wake deficits than prepro-orexin null mice. This phenotype is quite similar to that seen in constitutive OX2R null mice. These electrophysiological and behavioral deficits are fully restored after crossing OX2R mice with Zp3-Cre mice, which express Cre recombinase in the female germline.

OX1/2R TD progeny from crosses with OX1R TD mice (see Stock No. 027706) have severely fragmented sleep/wake behavior, similar to that seen in prepro-orexin null mice.

OX2R TD mice are useful as OX2R null mice in their native state. More importantly, they can be used to study the effects of focal or global restoration of OX2R signaling, using methods that produce focal or germline expression of Cre recombinase, respectively. Focal OX2R restoration can be used to test whether OX2R signaling in a specific brain region is sufficient to rescue specific behaviors.

Development

A floxed transcription disrupter cassette was inserted into intron 1 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

View All References

Genetics

Hcrtr2^tm1Tesc

Allele Symbol: Hcrtr2^tm1Tesc

Allele Name	targeted mutation 1, Thomas E Scammell
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	targeted mutation 1, Thomas E Scammell; Hcrtr2^tm1Tesc
Gene Symbol and Name	Hcrtr2, hypocretin (orexin) receptor 2
Gene Synonym(s)	mOXR2; OX2R; mOX2aR; mOX2bR; OX2r
Strain of Origin	129
Chromosome	9
Molecular Note	A floxed transcription disrupter cassette was inserted into intron 1, 137 bp upstream of exon 2 via homologous recombination. The transcription disrupter cassette includes an engrailed 2 splice acceptor, SV40 enhancer, Neo, and a Myc-associated zinc finger protein-binding site. RT-PCR analysis confirmed the absence of full length transcript and the presence of a mutant mRNA.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

narcolepsy

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: Hcrtr2^tm1Tesc/Hcrtr2^tm1Tesc
B6.Cg-Hcrtr2

behavior/neurological phenotype

abnormal depression-related behavior
- significant increase in total time spent immobile in the forced swim and tail suspension tests suggesting an increase in depression like behavior

fragmentation of sleep/wake states
- Normal - however, hourly amounts of wake, non-REM and REM sleep are normal
- wake and non-REM sleep bouts are shorter and more frequent, especially during the dark period

narcolepsy

mammalian phenotype

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

muscle phenotype

abnormal muscle tone
- cataplexy is very rare

nervous system phenotype

abnormal neuron physiology
- tuberomammillary nucleus neurons fail to respond to orexin-A unlike wild-type mice which respond with an increase in their firing rate associated with membrane depolarization

Genotype: Hcrtr2^tm1Tesc/Hcrtr2^tm1Tesc
B6.129-Hcrtr2

behavior/neurological phenotype

fragmentation of sleep/wake states
- bilateral microinjection of AAV-Cre dorsal into the posterior thalamus region fails to improve wakefulness
- mice with bilateral microinjection of AAV-Cre into the tuberomammillary nucleus region still have fragmented sleep with shorter non-REM bouts

mammalian phenotype

behavior/neurological phenotype
- Normal - following bilateral microinjection of AAV-Cre into the tuberomammillary nucleus region maintenance of wakefulness is markedly improved compared to non-Cre treated

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 - Hcrtr2^tm1Tesc related

Technical Support

Contact Technical Support

Genotyping Protocols
- MELT: Hcrtr2^tm1Tesc alternate1
- Genotyping resources and troubleshooting
Breeding Considerations

Homozygotes and heterozygotes are viable and fertile.
- Additional Breeding and Husbandry Support
Citation
When using the Hcrtr2 null mouse strain in a publication, please cite the originating article(s) and include JAX stock #027707 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 wildtype for Hcrtr2<tm1Tesc>

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.

Related Products and Services

Frozen Mouse Embryo

$2,595.00 per straw or vial

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.

Terms Of Use

Terms of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Also Known As: Hcrtr2 null, OX2R TD

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Hcrtr2tm1Tesc

Allele Symbol: Hcrtr2tm1Tesc

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Hcrtr2tm1Tesc/Hcrtr2tm1TescB6.Cg-Hcrtr2

behavior/neurological phenotype

mammalian phenotype

muscle phenotype

nervous system phenotype

Genotype: Hcrtr2tm1Tesc/Hcrtr2tm1TescB6.129-Hcrtr2

behavior/neurological phenotype

mammalian phenotype

References

Additional - Hcrtr2tm1Tesc 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

Related Products and Services

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

Hcrtr2^tm1Tesc

Allele Symbol: Hcrtr2^tm1Tesc

Genotype: Hcrtr2^tm1Tesc/Hcrtr2^tm1Tesc
B6.Cg-Hcrtr2

Genotype: Hcrtr2^tm1Tesc/Hcrtr2^tm1Tesc
B6.129-Hcrtr2

Additional - Hcrtr2^tm1Tesc related