Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation ?+N1p (15-MAY-05) Generation Definitions   Donating Investigator Patrik Ernfors,   Karolinska Institute

Description
Mice that are homozygous for the targeted mutation are viable, fertile and do not display any gross physical or behavioral abnormalities. By 1 month of age, mutant mice exhibit mild obesity. High-fat (Western) diet enhances the weight increase in female mutants. Northern blot analysis of hypothalamus detects mRNA encoding beta-galactosidase and not the endogenous mRNA. Beta galactosidase activity pattern mimic the endogenous gene expression pattern. Y2 receptor binding experiments confirm loss of activity. Mice homozygous for the mutation have increased night time basal heart rate compared to wildtype and exhibit reduced activity levels. Increased food intake is observed. Short term leptin administration elicits a decreased response of 15.2% food intake reduction compared to the 30.5% reduction seen in wildtype controls. Mutant mice are more sensitive to sodium Phenobarbital-induced sedation. Treatment with neuropeptide Y does not induce angiogenesis in the cornea. Wound healing in the skin is delayed with reduced neovascularization. This mutant mouse strain may be useful in studies of the role of the neuropeptide Y receptor and the physiological effects of neuropeptide Y.

Development
A targeting vector containing an internal ribosome entry site (IRES)-tau-lacZ fusion gene, and neomycin resistance gene and herpes simplex virus thymidine kinase genes was used to disrupt the protein encoding exon. The construct was electroporated into 129P2/OlaHsd derived HM-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to BALB/c mice, and then intercrossed to produce homozygotes.

Control Information

	Control
	See control note:	This strain is a mixture of BALB/c and 129P2/OlaHsd strains. There is no appropriate control for this strain.
	Wild-type from the colony
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Npy2r^tm1Pern/Npy2r^tm1Pern

        involves: 129/Sv * BALB/c

• adipose tissue phenotype
• increased total fat pad weight   (MGI Ref ID J:57961)
• behavior/neurological phenotype
• abnormal circadian regulation of heart rate
  • increase shows statistical significance at night   (MGI Ref ID J:57961)
• abnormal food intake
  • mutants show an attenuated response to leptin, exhibiting only a 15.2% reduction in food intake compared to 30.5% decrease in wild-type mice, 12 hours after leptin administration, however no differences in food intake are observed after 45 hours   (MGI Ref ID J:57961)
• • polyphagia
    • mean 12% increase in 24-hour food consumption   (MGI Ref ID J:57961)
• hypoactivity
  • reduction in activity during both dark and light phases   (MGI Ref ID J:57961)
• cardiovascular system phenotype
• abnormal circadian regulation of heart rate
  • increase shows statistical significance at night   (MGI Ref ID J:57961)
• growth/size phenotype
• increased body weight
  • males and females fed a normal-fat diet are mildly overweight   (MGI Ref ID J:57961)
  • a high-fat diet leads to a more substantial increase in body weight, especially in females   (MGI Ref ID J:57961)
• homeostasis/metabolism phenotype
• decreased energy expenditure
  • reduction in energy consumption as indicated by reduced activity during both light and dark phases   (MGI Ref ID J:57961)

Npy2r^tm1Pern/Npy2r^tm1Pern

        involves: 129/Sv * BALB/cJ

• behavior/neurological phenotype
• alcohol aversion
  • mice drink less 3% and 6% ethanol solution than wild-type mice   (MGI Ref ID J:102430)
• increased fluid intake
  • water consumption is increased relative to wild-type mice   (MGI Ref ID J:102430)

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

Npy2r^tm1Pern/Npy2r^tm1Pern

        involves: 129/Sv

• behavior/neurological phenotype
• abnormal sleep pattern
  • mice sleep longer than wild-type mice following treatment with pentobarbital   (MGI Ref ID J:71826)
• altered righting response
  • 50 mg/kg and 60 mg/kg of sodium pentobarbital induces a greater loss of righting reflex (LORR) than in wild-type mice (135% and143%, respectively by dose)   (MGI Ref ID J:71826)
  • however, righting response is no different from that of wild-type mice after treatment with ketamin   (MGI Ref ID J:71826)
  • NPY-induced sensitization to LORR induced by pentobarbital or ketamine is increased compared to in wild-type mice   (MGI Ref ID J:71826)
  • NPY-induced sensitization to LORR induced by pentobarbital greater when NPY is injected into the posterior hypothalamus versus the lateral hypothalamus   (MGI Ref ID J:71826)

View Research Applications

Research Applications

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

Internal/Organ Research
Wound Healing
      delayed/impaired

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

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Npy2rtm1Pern
Allele Name		targeted mutation 1, Patrick Ernfors
Allele Type		Targeted (Reporter)
Common Name(s)		Npy2r-; Y2-;
Mutation Made By		Patrik Ernfors,   Karolinska Institute
Strain of Origin		129/Sv
Gene Symbol and Name		Npy2r, neuropeptide Y receptor Y2
Chromosome		3
Gene Common Name(s)		NPY-Y2 receptor; NPY2-R;
Molecular Note		The gene was disrupted by insertion of a lacZ-neo cassette into a protein-coding exon via homologous recombination. Absence of gene expression was confirmed by Northern blot analysis of hypothalamus RNA. [MGI Ref ID J:109294] [MGI Ref ID J:57961]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Naveilhan P; Hassani H; Canals JM; Ekstrand AJ; Larefalk A; Chhajlani V; Arenas E; Gedda K; Svensson L; Thoren P; Ernfors P. 1999. Normal feeding behavior, body weight and leptin response require the neuropeptide Y Y2 receptor. Nat Med 5(10):1188-93. [PubMed: 10502824]  [MGI Ref ID J:57961]

Additional References

Npy2r^tm1Pern related

Ekstrand AJ; Cao R; Bjorndahl M; Nystrom S; Jonsson-Rylander AC; Hassani H; Hallberg B; Nordlander M; Cao Y. 2003. Deletion of neuropeptide Y (NPY) 2 receptor in mice results in blockage of NPY-induced angiogenesis and delayed wound healing. Proc Natl Acad Sci U S A 100(10):6033-8. [PubMed: 12730369]  [MGI Ref ID J:99821]

Fetissov SO; Byrne LC; Hassani H; Ernfors P; Hokfelt T. 2004. Characterization of neuropeptide Y Y2 and Y5 receptor expression in the mouse hypothalamus. J Comp Neurol 470(3):256-65. [PubMed: 14755515]  [MGI Ref ID J:109294]

Kuo LE; Kitlinska JB; Tilan JU; Li L; Baker SB; Johnson MD; Lee EW; Burnett MS; Fricke ST; Kvetnansky R; Herzog H; Zukowska Z. 2007. Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome. Nat Med 13(7):803-11. [PubMed: 17603492]  [MGI Ref ID J:125084]

Lee EW; Grant DS; Movafagh S; Zukowska Z. 2003. Impaired angiogenesis in neuropeptide Y (NPY)-Y2 receptor knockout mice. Peptides 24(1):99-106. [PubMed: 12576090]  [MGI Ref ID J:102431]

Mikic B; Zhang M; Webster E; Rossmeier K. 2008. Effect of y2 receptor deletion on whole bone structural behavior in mice. Anat Rec (Hoboken) 291(1):14-8. [PubMed: 18085606]  [MGI Ref ID J:174263]

Naveilhan P; Canals JM; Arenas E; Ernfors P. 2001. Distinct roles of the Y1 and Y2 receptors on neuropeptide Y-induced sensitization to sedation. J Neurochem 78(6):1201-7. [PubMed: 11579129]  [MGI Ref ID J:71826]

Naveilhan P; Svensson L; Nystrom S; Ekstrand AJ; Ernfors P. 2002. Attenuation of hypercholesterolemia and hyperglycemia in ob/ob mice by NPY Y2 receptor ablation. Peptides 23(6):1087-91. [PubMed: 12126735]  [MGI Ref ID J:102651]

Soscia SJ; Harrington ME. 2005. Neuropeptide Y does not reset the circadian clock in NPY Y2-/- mice. Neurosci Lett 373(3):175-8. [PubMed: 15619538]  [MGI Ref ID J:124448]

Thiele TE; Naveilhan P; Ernfors P. 2004. Assessment of ethanol consumption and water drinking by NPY Y(2) receptor knockout mice. Peptides 25(6):975-83. [PubMed: 15203244]  [MGI Ref ID J:102430]

Woldbye DP; Nanobashvili A; Sorensen AT; Husum H; Bolwig TG; Sorensen G; Ernfors P; Kokaia M. 2005. Differential suppression of seizures via Y2 and Y5 neuropeptide Y receptors. Neurobiol Dis 20(3):760-72. [PubMed: 15979311]  [MGI Ref ID J:104663]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as homozygotes. By 1 month of age, mutant mice exhibit mild obesity.
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	See control note:	This strain is a mixture of BALB/c and 129P2/OlaHsd strains. There is no appropriate control for this strain.
	Wild-type from the colony
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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