Strain Name:

B6.129-Htr2ctm1Jke/J

Stock Number:

015821

Order this mouse

Availability:

Repository- Live

These mutant mice contain a loxP-flanked transcriptional blocker cassette inserted between exon 3 and 4 of the Htr2c gene. The floxed-transcriptional blocker cassette abolishes gene function. When these mutant mice are bred to mice that express Cre recombinase, the resulting offspring will have the floxed-transcriptional blocker cassette removed, resulting in rescued Htr2c gene function. These mice may be useful for studying serotonin induced appetite suppression in obesity and diabetes.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating SystemHeterozygote x +/+ sibling         (Female x Male)   26-JUL-11
Specieslaboratory mouse
GenerationN10+F4 (06-MAR-13)
Generation Definitions
 
Donating Investigator Joel K Elmquist,   UT Southwestern Med Center at Dallas

Description
loxTB 5-Ht2CR mice contain a loxP-flanked transcriptional blocker cassette inserted between exons 3 and 4 of the 5-hydroxytryptamine (serotonin) receptor 2C (Htr2c) gene. The floxed-transcriptional blocker cassette abolishes gene function. Homozygous females and hemizygous males are fertile and normal in size. Hemizygous males have a high mortality rate due to seizures. Htr2c, an X-linked gene, is a serotonin receptor expressed in pro-opiomelanocortin neurons and plays a crucial role in the regulation of energy homeostasis and appetite suppression. Serotonin activates this receptor and suppresses appetite. These mice lack Htr2c expression in the cerebral cortex, hypothalamus, arcuate nucleus of hypothalamus, and the brainstem. They are hyperphagic, exhibiting a 50% increase in weekly food intake compared to wild-type littermates. They also develop late-onset hyperleptinemia, leptin insensitivity, and obesity which is accelerated on a high fat diet. These loxTB 5-Ht2CR mice display an increase in fat mass and a decrease in lean mass. When these mutant mice are bred to mice that express Cre recombinase, the resulting offspring will have the floxed-transcriptional blocker cassette removed, resulting in rescued Htr2c gene function. These mice may be useful for studying serotonin induced appetite suppression in obesity and diabetes.

Development
A targeting vector was designed to insert a loxP-flanked transcriptional blocker cassette, containing a simian virus 40 (SV40) promoter, a neomycin (neo) resistance gene, and the polyadenylation sequence, between exon 3 and 4 of the 5-hydroxytryptamine (serotonin) receptor 2C (Htr2c) gene. The construct was electroporated into 129-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6J females to generate a colony of loxTB 5-Ht2CR mice. The donating investigator reported that these mice were backcrossed for at least 9 generations to C57BL/6J background (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While most of the 27 markers throughout the genome suggested a C57BL/6 genetic background, markers on Chromosomes 6, 11, and 15 were found to be segregating. Also, 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed genetic background.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Htr2c
002627   B6.129-Htr2ctm1Jul/J
View Strains carrying other alleles of Htr2c     (1 strain)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Htr2ctm1Jke/Y

        B6.129-Htr2ctm1Jke
  • mortality/aging
  • premature death
    • mice exhibit a decreased survival rate compared to wild-type mice   (MGI Ref ID J:147514)
    • mice fed a regular diet exhibit decreased survival compared to mice fed a high fat diet   (MGI Ref ID J:147514)
  • adipose tissue phenotype
  • increased percent body fat
    • when fed a high fat diet, mice exhibit increased adiposity compared to similarly treated wild-type mice as early as 13 weeks and at 28 weeks   (MGI Ref ID J:147514)
  • increased white adipose tissue amount
    • when fed a high fat diet, mice exhibit an increase in visceral and subcutaneous depots compared to in similarly wild-type mice   (MGI Ref ID J:147514)
  • behavior/neurological phenotype
  • hyperactivity
    • when fed a normal diet, mice exhibit hyperactivity compared to wild-type mice without an increase in energy expenditure   (MGI Ref ID J:147514)
  • impaired behavioral response to xenobiotic
    • mice treated with d-Fen fail to exhibit reduced food intake as do similarly treated wild-type mice   (MGI Ref ID J:147514)
    • mice treated with metachlorophenylpiperazine exhibit a blunted response compared to similarly treated wild-type mice that exhibit a decrease in food intake   (MGI Ref ID J:147514)
  • polyphagia
    • mice are hyperphagic compared to wild-type mice   (MGI Ref ID J:147514)
    • on a high fat diet, mice exhibit a 50% increase in food intake compared to similarly treated wild-type mice   (MGI Ref ID J:147514)
    • meal sizes are larger than for wild-type mice   (MGI Ref ID J:147514)
    • however, meal frequency is normal   (MGI Ref ID J:147514)
  • tonic-clonic seizures   (MGI Ref ID J:147514)
  • homeostasis/metabolism phenotype
  • increased circulating leptin level
    • when fed a high fat diet   (MGI Ref ID J:147514)
  • increased susceptibility to diet-induced obesity
    • when fed a high fat diet   (MGI Ref ID J:147514)
  • growth/size/body phenotype
  • decreased lean body mass   (MGI Ref ID J:147514)
  • increased percent body fat
    • when fed a high fat diet, mice exhibit increased adiposity compared to similarly treated wild-type mice as early as 13 weeks and at 28 weeks   (MGI Ref ID J:147514)
  • increased susceptibility to diet-induced obesity
    • when fed a high fat diet   (MGI Ref ID J:147514)
  • nervous system phenotype
  • tonic-clonic seizures   (MGI Ref ID J:147514)
View Research Applications

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

Diabetes and Obesity Research
Obesity With Diabetes
      adult onset
      diet-induced

Neurobiology Research
Cre-lox System
      loxP-flanked Sequences

Research Tools
Diabetes and Obesity Research
      loxP

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Htr2ctm1Jke
Allele Name targeted mutation 1, Bradford B Lowell
Allele Type Targeted (knock-in)
Common Name(s) 2C null; loxTB 5-HT2CR;
Mutation Made By Joel Elmquist,   UT Southwestern Med Center at Dallas
Strain of Origin129
Promoter Htr2c, 5-hydroxytryptamine (serotonin) receptor 2C, mouse, laboratory
Molecular Note A floxed transcription blocker cassette (loxTB) was inserted between exons 3 and 4. Expression is disrupted unless reactivated by cre mediated recombination. The absence of transcript expression was confirmed by RT-PCR on cerebral cortex, whole hypothalamus, arcuate nucleus of the hypothalamus, and brainstem extracts. [MGI Ref ID J:147514]

Genotyping

Genotyping Information

Genotyping Protocols

Htr2ctm1Jke, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Xu Y; Jones JE; Kohno D; Williams KW; Lee CE; Choi MJ; Anderson JG; Heisler LK; Zigman JM; Lowell BB; Elmquist JK. 2008. 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis. Neuron 60(4):582-9. [PubMed: 19038216]  [MGI Ref ID J:147514]

Additional References

Htr2ctm1Jke related

Sohn JW; Xu Y; Jones JE; Wickman K; Williams KW; Elmquist JK. 2011. Serotonin 2C Receptor Activates a Distinct Population of Arcuate Pro-opiomelanocortin Neurons via TRPC Channels. Neuron 71(3):488-97. [PubMed: 21835345]  [MGI Ref ID J:174678]

Xu Y; Berglund ED; Sohn JW; Holland WL; Chuang JC; Fukuda M; Rossi J; Williams KW; Jones JE; Zigman JM; Lowell BB; Scherer PE; Elmquist JK. 2010. 5-HT(2C)Rs expressed by pro-opiomelanocortin neurons regulate insulin sensitivity in liver. Nat Neurosci 13(12):1457-9. [PubMed: 21037584]  [MGI Ref ID J:166904]

Xu Y; Jones JE; Lauzon DA; Anderson JG; Balthasar N; Heisler LK; Zinn AR; Lowell BB; Elmquist JK. 2010. A serotonin and melanocortin circuit mediates D-fenfluramine anorexia. J Neurosci 30(44):14630-4. [PubMed: 21048120]  [MGI Ref ID J:166702]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB27

Colony Maintenance

Breeding & HusbandryThe flox-STOP mutation is on the X chromosome. When maintaining a live colony, homozygous females may be bred to wildtype males or to C57BL/6J (Stock No. 000664) inbred males. The donating investigator reports that hemizygous males have decreased survival due to seizures.
Mating SystemHeterozygote x +/+ sibling         (Female x Male)   26-JUL-11

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00MaleHemizygous for Htr2ctm1Jke  
$232.00FemaleHeterozygous for Htr2ctm1Jke  
Price per Pair (US dollars $)Pair Genotype
$302.00Heterozygous for Htr2ctm1Jke x Wild-type for Htr2ctm1Jke  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60MaleHemizygous for Htr2ctm1Jke  
$301.60FemaleHeterozygous for Htr2ctm1Jke  
Price per Pair (US dollars $)Pair Genotype
$392.60Heterozygous for Htr2ctm1Jke x Wild-type for Htr2ctm1Jke  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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.


See Terms of Use tab for General Terms and Conditions


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.
Ordering Information
JAX® Mice
Surgical and Preconditioning Services
JAX® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use


General Terms and Conditions


Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:207-288-6470

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"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "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 the 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 or PRODUCTS 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.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

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 and PRODUCTS 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.


(6.5)