Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6 Donor Strain (129) Generation N7p   Donating Investigator David Julius,   Univ of California at San Francisco

Description
Homozygous mice show spontaneous and infrequent epileptic seizures, sometimes resulting in death. They also show overeating behavior and an increase in the accumulation of white adipose tissue.

Development
This strain was developed in the laboratory of Dr. David Julius at University of California at San Francisco. A routine Genetic Quality Control assessment of the strain's genetic background was performed (6/2005) using a panel of 27 Single Nucleotide Polymorphism (SNP) markers. The SNP markers used distinguish between the inbred mouse strain backgrounds found at The Jackson Laboratory (TJL). Our findings indicate that portions of chromosome 1 (region of 52.0 cM) and chromosome X (region of 21.9 cM) are derived from the 129 donor strain genetic background. The targeted gene is located at 66.15 cM on the X chromosome. This strain was imported into the Induced Mutant Resource at TJL in 1997. It was assigned a congenic strain designation based upon guidelines offered by International Committee on Standardized Genetic Nomenclature for Mice, in conjunction with information provided by the donating investigator that the imported mice had been backcrossed to C57BL/6J at least 5 times (N5).

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

	Body Mass Index Quantitative Trait Locus 11; BMIQ11 - Models with phenotypic similarity to human disease where etiologies are distinct.2
	Diabetes Mellitus, Noninsulin-Dependent; NIDDM - Models with phenotypic similarity to human disease where etiologies are distinct.2

2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Htr2c^tm1Jul/Y

        B6.129S2-Htr2c^tm1Jul

• behavior/neurological phenotype
• abnormal response to new environment (MGI Ref ID J:51567)
  • mutants show reduced aversion to a novel environment; the latencies to emerge from a small dark enclosure into a brightly lit open field are reduced in mutants compared to wild-type
• abnormal spatial learning (MGI Ref ID J:51567)
  • mutants show abnormal performance in the Morris water maze, failing to show a preference for the trained site in probe trials following training
  • however contextual conditioning is normal
• nervous system phenotype
• reduced long term potentiation (MGI Ref ID J:51567)
  • selective impairment of long-term potentiation restricted to medial perforant path-dentate gyrus synapses of mutants, indicating perturbed dentate gyrus function

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Htr2c^tm1Jul/Y

        involves: 129S2/SvPas * C57BL/6 * DBA/2

• life span-post-weaning/aging
• premature death (MGI Ref ID J:24339)
  • less than 60% survival at 25 weeks
• growth/size phenotype
• increased body mass index (MGI Ref ID J:24339)
  • obesity, 13% increase in total body mass
• adipose tissue phenotype
• increased white adipose tissue amount (MGI Ref ID J:24339)
  • 48% increase in depostion of perirenal white adipose tissue
• behavior/neurological phenotype
• polyphagia (MGI Ref ID J:24339)
  • increased food consumption
• seizures (MGI Ref ID J:24339)
  • epileptic seizures, may be cause of premature death
• homeostasis/metabolism phenotype
• increased circulating insulin level (MGI Ref ID J:50262)
  • hyperinsulinemia, hyperleptinemia at 39 - 43 weeks
• increased circulating leptin level (MGI Ref ID J:50262)
  • hyperleptinemia at 39 - 43 weeks
• nervous system phenotype
• seizures (MGI Ref ID J:24339)
  • epileptic seizures, may be cause of premature death

View Research Applications

Research Applications

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

Neurobiology Research
Receptor Defects (serotonin)

Htr2c^tm1Jul related

Diabetes and Obesity Research
Obesity Without Diabetes (moderate, adult onset)

Neurobiology Research
Behavioral and Learning Defects
Epilepsy
Neurotransmitter Receptor and Synaptic Vesicle Defects
Receptor Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Htr2ctm1Jul
Allele Name		targeted mutation 1, David Julius
Allele Type		Targeted (knock-out)
Common Name(s)		5-HT2cR-deficient;
Mutation Made By		David Julius,   Univ of California at San Francisco
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Htr2c, 5-hydroxytryptamine (serotonin) receptor 2C
Chromosome		X
Gene Common Name(s)		5-HT2C; 5-HT2C receptor; 5-HT2cR; 5-HTR2C; 5-hydroxytryptamine (serotonin) receptor 1C; 5HT-1C; 5HT1c; HTR1C; Htr1c; SR1;
Molecular Note		Insertion of a nonsense mutation into exon 5 of the gene resulted in the introduction of a stop codon within the fifth putative transmembrane segment of the receptor and in the elimination of the carboxy-terminal half of the protein. [MGI Ref ID J:24339]

Genotyping

Genotyping Information

Genotyping Protocols

Htr2c^tm1Jul, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Tecott LH; Sun LM; Akana SF; Strack AM; Lowenstein DH; Dallman MF; Julius D. 1995. Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors [see comments] Nature 374(6522):542-6. [PubMed: 7700379]  [MGI Ref ID J:24339]

Additional References

Htr2c^tm1Jul related

Akana SF. 2008. Feeding and stress interact through the serotonin 2C receptor in developing mice. Physiol Behav 94(4):569-79. [PubMed: 18495184]  [MGI Ref ID J:139775]

Applegate CD; Tecott LH. 1998. Global increases in seizure susceptibility in mice lacking 5-HT2C receptors: a behavioral analysis. Exp Neurol 154(2):522-30. [PubMed: 9878187]  [MGI Ref ID J:52051]

Brennan TJ; Seeley WW; Kilgard M; Schreiner CE; Tecott LH. 1997. Sound-induced seizures in serotonin 5-HT2c receptor mutant mice. Nat Genet 16(4):387-90. [PubMed: 9241279]  [MGI Ref ID J:42053]

Chou-Green JM; Holscher TD; Dallman MF; Akana SF. 2003. Compulsive behavior in the 5-HT2C receptor knockout mouse. Physiol Behav 78(4-5):641-9. [PubMed: 12782219]  [MGI Ref ID J:96440]

Chou-Green JM; Holscher TD; Dallman MF; Akana SF. 2003. Repeated stress in young and old 5-HT(2C) receptor knockout mice. Physiol Behav 79(2):217-26. [PubMed: 12834793]  [MGI Ref ID J:96453]

Frank MG; Stryker MP; Tecott LH. 2002. Sleep and sleep homeostasis in mice lacking the 5-HT2c receptor. Neuropsychopharmacology 27(5):869-73. [PubMed: 12431861]  [MGI Ref ID J:106164]

Heisler LK; Pronchuk N; Nonogaki K; Zhou L; Raber J; Tung L; Yeo GS; O'Rahilly S; Colmers WF; Elmquist JK; Tecott LH. 2007. Serotonin activates the hypothalamic-pituitary-adrenal axis via serotonin 2C receptor stimulation. J Neurosci 27(26):6956-64. [PubMed: 17596444]  [MGI Ref ID J:122977]

Heisler LK; Tecott LH. 2000. A paradoxical locomotor response in serotonin 5-HT(2C) receptor mutant mice. J Neurosci 20(8):RC71. [PubMed: 10751458]  [MGI Ref ID J:121198]

Heisler LK; Zhou L; Bajwa P; Hsu J; Tecott LH. 2007. Serotonin 5-HT(2C) receptors regulate anxiety-like behavior. Genes Brain Behav 6(5):491-6. [PubMed: 17451451]  [MGI Ref ID J:137308]

Lin L; York DA. 2005. 5-HT1B receptors modulate the feeding inhibitory effects of enterostatin. Brain Res 1062(1-2):26-31. [PubMed: 16256085]  [MGI Ref ID J:103466]

Lopez-Gimenez JF; Tecott LH; Palacios JM; Mengod G; Vilaro MT. 2002. Serotonin 5- HT (2C) receptor knockout mice: autoradiographic analysis of multiple serotonin receptors. J Neurosci Res 67(1):69-85. [PubMed: 11754082]  [MGI Ref ID J:104818]

Memon RA; Tecott LH; Nonogaki K; Beigneux A; Moser AH; Grunfeld C; Feingold KR. 2000. Up-regulation of peroxisome proliferator-activated receptors (PPAR-alpha) and PPAR-gamma messenger ribonucleic acid expression in the liver in murine obesity: troglitazone induces expression of PPAR-gamma-responsive adipose tissue-specific genes in the liver of obese diabetic mice [In Process Citation] Endocrinology 141(11):4021-31. [PubMed: 11089532]  [MGI Ref ID J:65569]

Nonogaki K; Abdallah L; Goulding EH; Bonasera SJ; Tecott LH. 2003. Hyperactivity and Reduced Energy Cost of Physical Activity in Serotonin 5-HT(2C) Receptor Mutant Mice. Diabetes 52(2):315-20. [PubMed: 12540602]  [MGI Ref ID J:81611]

Nonogaki K; Memon RA; Grunfeld C; Feingold KR; Tecott LH. 2002. Altered gene expressions involved in energy expenditure in 5-HT(2C) receptor mutant mice. Biochem Biophys Res Commun 295(2):249-54. [PubMed: 12150939]  [MGI Ref ID J:108471]

Nonogaki K; Ohba Y; Sumii M; Oka Y. 2008. Serotonin systems upregulate the expression of hypothalamic NUCB2 via 5-HT2C receptors and induce anorexia via a leptin-independent pathway in mice. Biochem Biophys Res Commun 372(1):186-90. [PubMed: 18477467]  [MGI Ref ID J:136954]

Nonogaki K; Strack AM; Dallman MF; Tecott LH. 1998. Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene [see comments] Nat Med 4(10):1152-6. [PubMed: 9771748]  [MGI Ref ID J:50262]

Rocha BA; Goulding EH; O'Dell LE; Mead AN; Coufal NG; Parsons LH; Tecott LH. 2002. Enhanced locomotor, reinforcing, and neurochemical effects of cocaine in serotonin 5-hydroxytryptamine 2C receptor mutant mice. J Neurosci 22(22):10039-45. [PubMed: 12427861]  [MGI Ref ID J:80185]

Tecott LH; Logue SF; Wehner JM; Kauer JA. 1998. Perturbed dentate gyrus function in serotonin 5-HT2C receptor mutant mice. Proc Natl Acad Sci U S A 95(25):15026-31. [PubMed: 9844009]  [MGI Ref ID J:51567]

Toth M; Tecott L. 1999. Transgenic approaches to epilepsy. Adv Neurol 79:291-6. [PubMed: 10514821]  [MGI Ref ID J:59737]

Vickers SP; Clifton PG; Dourish CT; Tecott LH. 1999. Reduced satiating effect of d-fenfluramine in serotonin 5-HT(2C) receptor mutant mice. Psychopharmacology (Berl) 143(3):309-14. [PubMed: 10353435]  [MGI Ref ID J:57205]

Wade JM; Juneja P; MacKay AW; Graham J; Havel PJ; Tecott LH; Goulding EH. 2008. Synergistic impairment of glucose homeostasis in ob/ob mice lacking functional serotonin 2C receptors. Endocrinology 149(3):955-61. [PubMed: 18039786]  [MGI Ref ID J:135963]

Wang B; Chehab FF. 2006. Deletion of the serotonin 2c receptor from transgenic mice overexpressing leptin does not affect their lipodystrophy but exacerbates their diet-induced obesity. Biochem Biophys Res Commun 351(2):418-23. [PubMed: 17064660]  [MGI Ref ID J:116543]

Yang Y; Mahaffey CL; Berube N; Maddatu TP; Cox GA; Frankel WN. 2007. Complex seizure disorder caused by Brunol4 deficiency in mice. PLoS Genet 3(7):e124. [PubMed: 17677002]  [MGI Ref ID J:123744]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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.

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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.