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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
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Description
Strain Information
Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote (Female x Male) 01-MAR-06 Species laboratory mouse Generation N?+F?+F11 (24-DEC-08) Donating Investigator Richard Palmiter, University of Washington Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by Northern or Western blot analysis of brain or adrenal gland tissue. Beta-galactosidase activity assays and in situ hybridization demonstrate similar expression patterns for the lacZ gene and the endogenous wildtype gene. Spontaneous seizures are exhibited by some mice at age 6 to 8 weeks. Homozygous mice are susceptible to seizures induced by GABA antagonist treatment. Mutant mice have an increased sensitivity to leptin treatment which results in a greater initial reduction of food intake and weight loss when compared to wildtype mice. This mutant mouse strain may be useful in studies related to the role of neuropeptide Y in obesity.Development
A targeting vector containing neomycin resistance, thymidine kinase and lacZ reporter genes was used to disrupt exon 2 of the targeted gene. The construct was electroporated into 129S7/SvEvBrd-Hprt+ derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.
Control Information
| Control | ||
|---|---|---|
| 002448 129S1/SvImJ | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (186 strains)
008321 B6.Cg-Tg(Npy-MAPT/GFP*)1Rck/J 006417 B6.FVB-Tg(Npy-hrGFP)1Lowl/J 007585 B6;129S4-Npytm2Rpa/J
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
Npytm1Rpa/Npytm1Rpa
involves: 129S7/SvEvBrd
- behavior/neurological phenotype
- increased susceptibility to pharmacologically induced seizures (MGI Ref ID J:33261)
- pentylenetrazole (PTZ) treatment at 50 or 60 mg/kg induced convulsions in 80% of mutant mice compared to 33% of controls
- convulsions in the mutant mice were also scored as more severe
- sporadic seizures (MGI Ref ID J:33261)
- mice exhibited occasional mild seizures at 6-8 weeks of age, with decreased frequency until 9 weeks and were not seen thereafter; seizures consisted of jerking of the head and body, tail extension and vocalization
- homeostasis/metabolism phenotype
- *normal* homeostasis/metabolism phenotype (MGI Ref ID J:33261)
- no defects were observed in food intake, body weight and adiposity
- normal glucose homeostasis was also noted
- responses to food deprivation was similar to controls
- nervous system phenotype
- increased susceptibility to pharmacologically induced seizures (MGI Ref ID J:33261)
- pentylenetrazole (PTZ) treatment at 50 or 60 mg/kg induced convulsions in 80% of mutant mice compared to 33% of controls
- convulsions in the mutant mice were also scored as more severe
- sporadic seizures (MGI Ref ID J:33261)
- mice exhibited occasional mild seizures at 6-8 weeks of age, with decreased frequency until 9 weeks and were not seen thereafter; seizures consisted of jerking of the head and body, tail extension and vocalization
This mouse can be used to support research in many areas including:
Npytm1Rpa relatedDiabetes and Obesity Research
Obesity Without Diabetes
leptin hypersensitive
Neurobiology Research
lacZ expression in neural tissue
Channel and Transporter Defects
Research Tools
lacZ Expression
Diabetes and Obesity Research
lacZ
Diabetes and Obesity Research
Obesity Without Diabetes
leptin hypersensitive
Neurobiology Research
Epilepsy
Research Tools
Neurobiology Research
cell marker
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Npytm1Rpa | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Richard D Palmiter | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | Npy-; | ||
| Mutation Made By | Richard Palmiter, University of Washington | ||
| Strain of Origin | 129S7/SvEvBrd-Hprt1<+> | ||
| ES Cell Line Name | AB1 | ||
| ES Cell Line Strain | 129S7/SvEvBrd-Hprt1<+> | ||
| Site of Expression | lacZ replaces/mimics endogenous gene expression | ||
| Gene Symbol and Name | Npy, neuropeptide Y | ||
| Chromosome | 6 | ||
| Gene Common Name(s) | 0710005A05Rik; NPY02; PYY4; RATNPY; RATNPY02; RIKEN cDNA 0710005A05 gene; | ||
| Molecular Note | Exon 2, which encodes the signal peptide and 35 amino acids, was replaced by a lacZ-neo fusion gene. The expression pattern of the beta-galactosidase was shown to resemble that of the endogenous gene via comparisons of X-gal staining and previous in situhybridization studies. RT-PCR analysis of brain tissue showed an absence of transcript in homozygous mutant mice. [MGI Ref ID J:33261] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Npytm1Rpa, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Erickson JC; Clegg KE; Palmiter RD. 1996. Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y [see comments] Nature 381(6581):415-21. [PubMed: 8632796] [MGI Ref ID J:33261]
Additional References
Npytm1Rpa relatedAnitha M; Chandrasekharan B; Salgado JR; Grouzmann E; Mwangi S; Sitaraman SV; Srinivasan S. 2006. Glial-derived neurotrophic factor modulates enteric neuronal survival and proliferation through neuropeptide Y. Gastroenterology 131(4):1164-78. [PubMed: 17030186] [MGI Ref ID J:124956]
Bannon AW; Seda J; Carmouche M; Francis JM; Norman MH; Karbon B; McCaleb ML. 2000. Behavioral characterization of neuropeptide Y knockout mice Brain Res 868(1):79-87. [PubMed: 10841890] [MGI Ref ID J:62886]
Baraban SC; Hollopeter G; Erickson JC; Schwartzkroin PA; Palmiter RD. 1997. Knock-out mice reveal a critical antiepileptic role for neuropeptide Y. J Neurosci 17(23):8927-36. [PubMed: 9364040] [MGI Ref ID J:44284]
Baskin DG; Seeley RJ; Kuijper JL; Lok S; Weigle DS; Erickson JC; Palmiter RD; Schwartz MW. 1998. Increased expression of mRNA for the long form of the leptin receptor in the hypothalamus is associated with leptin hypersensitivity and fasting. Diabetes 47(4):538-43. [PubMed: 9568684] [MGI Ref ID J:46631]
Chandrasekharan B; Bala V; Kolachala VL; Vijay-Kumar M; Jones D; Gewirtz AT; Sitaraman SV; Srinivasan S. 2008. Targeted deletion of neuropeptide Y (NPY) modulates experimental colitis. PLoS ONE 3(10):e3304. [PubMed: 18836554] [MGI Ref ID J:144421]
Chen HY; Trumbauer ME; Chen AS; Weingarth DT; Adams JR; Frazier EG; Shen Z; Marsh DJ; Feighner SD; Guan XM; Ye Z; Nargund RP; Smith RG; Van der Ploeg LH; Howard AD; MacNeil DJ; Qian S. 2004. Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein. Endocrinology 145(6):2607-12. [PubMed: 14962995] [MGI Ref ID J:90744]
Doyle KL; Karl T; Hort Y; Duffy L; Shine J; Herzog H. 2008. Y1 receptors are critical for the proliferation of adult mouse precursor cells in the olfactory neuroepithelium. J Neurochem 105(3):641-52. [PubMed: 18088353] [MGI Ref ID J:134462]
Elefteriou F; Takeda S; Liu X; Armstrong D; Karsenty G. 2003. Monosodium glutamate-sensitive hypothalamic neurons contribute to the control of bone mass. Endocrinology 144(9):3842-7. [PubMed: 12933656] [MGI Ref ID J:85588]
Erickson JC; Hollopeter G; Palmiter RD. 1996. Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y. Science 274(5293):1704-7. [PubMed: 8939859] [MGI Ref ID J:37106]
Gehlert DR; Shaw JL. 2007. Increased brain neuropeptide Y1 and Y2 receptor binding in NPY knock out mice does not result in increased receptor function. Peptides 28(2):241-9. [PubMed: 17208335] [MGI Ref ID J:124440]
Hansel DE; Eipper BA; Ronnett GV. 2001. Neuropeptide Y functions as a neuroproliferative factor. Nature 410(6831):940-4. [PubMed: 11309620] [MGI Ref ID J:68917]
Harrington M; Molyneux P; Soscia S; Prabakar C; McKinley-Brewer J; Lall G. 2007. Behavioral and neurochemical sources of variability of circadian period and phase: studies of circadian rhythms of npy-/- mice. Am J Physiol Regul Integr Comp Physiol 292(3):R1306-14. [PubMed: 17082354] [MGI Ref ID J:119102]
Hill JW; Levine JE. 2003. Abnormal response of the neuropeptide Y-deficient mouse reproductive axis to food deprivation but not lactation. Endocrinology 144(5):1780-6. [PubMed: 12697683] [MGI Ref ID J:115711]
Hohmann JG; Teklemichael DN; Weinshenker D; Wynick D; Clifton DK; Steiner RA. 2004. Obesity and endocrine dysfunction in mice with deletions of both neuropeptide Y and galanin. Mol Cell Biol 24(7):2978-85. [PubMed: 15024085] [MGI Ref ID J:89070]
Hollopeter G; Erickson JC; Palmiter RD. 1998. Role of neuropeptide Y in diet-, chemical- and genetic-induced obesity of mice. Int J Obes Relat Metab Disord 22(6):506-12. [PubMed: 9665670] [MGI Ref ID J:49932]
Kim HJ; Harrington ME. 2008. Neuropeptide Y-deficient mice show altered circadian response to simulated natural photoperiod. Brain Res 1246:96-100. [PubMed: 18926801] [MGI Ref ID J:147619]
Laskowski A; Howell OW; Sosuov AA; McKhann G; Gray WP. 2007. NPY mediates basal and seizure-induced proliferation in the subcallosal zone. Neuroreport 18(10):1005-8. [PubMed: 17558285] [MGI Ref ID J:123746]
Luque RM; Kineman RD; Tena-Sempere M. 2007. Regulation of hypothalamic expression of KiSS-1 and GPR54 genes by metabolic factors: analyses using mouse models and a cell line. Endocrinology 148(10):4601-11. [PubMed: 17595226] [MGI Ref ID J:129475]
Luque RM; Park S; Kineman RD. 2007. Severity of the catabolic condition differentially modulates hypothalamic expression of growth hormone-releasing hormone in the fasted mouse: potential role of neuropeptide Y and corticotropin-releasing hormone. Endocrinology 148(1):300-9. [PubMed: 17038558] [MGI Ref ID J:129559]
Minor RK; Villarreal J; McGraw M; Percival SS; Ingram DK; de Cabo R. 2008. Calorie restriction alters physical performance but not cognition in two models of altered neuroendocrine signaling. Behav Brain Res 189(1):202-211. [PubMed: 18291538] [MGI Ref ID J:132779]
Park S; Peng XD; Frohman LA; Kineman RD. 2005. Expression analysis of hypothalamic and pituitary components of the growth hormone axis in fasted and streptozotocin-treated neuropeptide Y (NPY)-intact (NPY+/+) and NPY-knockout (NPY-/-) mice. Neuroendocrinology 81(6):360-71. [PubMed: 16244497] [MGI Ref ID J:106620]
Patel HR; Qi Y; Hawkins EJ; Hileman SM; Elmquist JK; Imai Y; Ahima RS. 2006. Neuropeptide Y deficiency attenuates responses to fasting and high-fat diet in obesity-prone mice. Diabetes 55(11):3091-8. [PubMed: 17065347] [MGI Ref ID J:116549]
Phillips CT; Palmiter RD. 2008. Role of agouti-related protein-expressing neurons in lactation. Endocrinology 149(2):544-50. [PubMed: 17974621] [MGI Ref ID J:144616]
Protas L; Barbuti A; Qu J; Rybin VO; Palmiter RD; Steinberg SF; Robinson RB. 2003. Neuropeptide Y is an essential in vivo developmental regulator of cardiac ICa,L. Circ Res 93(10):972-9. [PubMed: 14525809] [MGI Ref ID J:135474]
Qian S; Chen H; Weingarth D; Trumbauer ME; Novi DE; Guan X; Yu H; Shen Z; Feng Y; Frazier E; Chen A; Camacho RE; Shearman LP; Gopal-Truter S; MacNeil DJ; Van der Ploeg LH; Marsh DJ. 2002. Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice. Mol Cell Biol 22(14):5027-35. [PubMed: 12077332] [MGI Ref ID J:78034]
Schwartz MW; Erickson JC; Baskin DG; Palmiter RD. 1998. Effect of fasting and leptin deficiency on hypothalamic neuropeptide Y gene transcription in vivo revealed by expression of a lacZ reporter gene. Endocrinology 139(5):2629-35. [PubMed: 9564880] [MGI Ref ID J:114273]
Segal-Lieberman G; Trombly DJ; Juthani V; Wang X; Maratos-Flier E. 2003. NPY ablation in C57BL/6 mice leads to mild obesity and to an impaired refeeding response to fasting. Am J Physiol Endocrinol Metab 284(6):E1131-9. [PubMed: 12582011] [MGI Ref ID J:83899]
Shannon HE; Yang L. 2004. Seizure susceptibility of neuropeptide-Y null mutant mice in amygdala kindling and chemical-induced seizure models. Epilepsy Res 61(1-3):49-62. [PubMed: 15451008] [MGI Ref ID J:101832]
Shi TJ; Zhang X; Berge OG; Erickson JC; Palmiter RD; Hokfelt T. 1998. Effect of peripheral axotomy on dorsal root ganglion neuron phenotype and autonomy behaviour in neuropeptide Y-deficient mice. Regul Pept 75-76:161-73. [PubMed: 9802405] [MGI Ref ID J:53172]
Sinclair JR; Jacobs AL; Nirenberg S. 2004. Selective ablation of a class of amacrine cells alters spatial processing in the retina. J Neurosci 24(6):1459-67. [PubMed: 14960619] [MGI Ref ID J:109725]
Sindelar DK; Mystkowski P; Marsh DJ; Palmiter RD; Schwartz MW. 2002. Attenuation of diabetic hyperphagia in neuropeptide Y--deficient mice. Diabetes 51(3):778-83. [PubMed: 11872679] [MGI Ref ID J:75023]
Sindelar DK; Palmiter RD; Woods SC; Schwartz MW. 2005. Attenuated feeding responses to circadian and palatability cues in mice lacking neuropeptide Y. Peptides 26(12):2597-602. [PubMed: 15923061] [MGI Ref ID J:106644]
Sindelar DK; Ste Marie L; Miura GI; Palmiter RD; McMinn JE; Morton GJ; Schwartz MW. 2004. Neuropeptide Y is required for hyperphagic feeding in response to neuroglucopenia. Endocrinology 145(7):3363-8. [PubMed: 15064281] [MGI Ref ID J:105627]
Sun QQ; Baraban SC; Prince DA; Huguenard JR. 2003. Target-specific neuropeptide Y-ergic synaptic inhibition and its network consequences within the mammalian thalamus. J Neurosci 23(29):9639-49. [PubMed: 14573544] [MGI Ref ID J:86308]
Thiele TE; Marsh DJ; Ste. Marie L; Bernstein IL; Palmiter RD. 1998. Ethanol consumption and resistance are inversely related to neuropeptide Y levels [see comments] Nature 396(6709):366-9. [PubMed: 9845072] [MGI Ref ID J:51243]
Thiele TE; Miura GI; Marsh DJ; Bernstein IL; Palmiter RD. 2000. Neurobiological responses to ethanol in mutant mice lacking neuropeptide Y or the Y5 receptor. Pharmacol Biochem Behav 67(4):683-91. [PubMed: 11166058] [MGI Ref ID J:102529]
Tschop M; Statnick MA; Suter TM; Heiman ML. 2002. GH-releasing peptide-2 increases fat mass in mice lacking NPY: indication for a crucial mediating role of hypothalamic agouti-related protein. Endocrinology 143(2):558-68. [PubMed: 11796511] [MGI Ref ID J:74978]
Weinshenker D; Szot P; Miller NS; Rust NC; Hohmann JG; Pyati U; White SS; Palmiter RD. 2001. Genetic comparison of seizure control by norepinephrine and neuropeptide Y. J Neurosci 21(19):7764-9. [PubMed: 11567066] [MGI Ref ID J:71685]
Xu M; Hill JW; Levine JE. 2000. Attenuation of luteinizing hormone surges in neuropeptide Y knockout mice Neuroendocrinology 72(5):263-71. [PubMed: 11124583] [MGI Ref ID J:66273]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry The resulting chimeric animals were crossed to 129S1/SvImJ mice. This strain is maintained as a homozygote. Mating System Homozygote x Homozygote (Female x Male) 01-MAR-06 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $107.90 Female or Male Homozygous for Npytm1Rpa
Pairs /Price (US dollars $) Pair Genotype $215.80 Homozygous for Npytm1Rpa x Homozygous for Npytm1Rpa
Additional Supply Details
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $140.30 Female or Male Homozygous for Npytm1Rpa
Pairs /Price (US dollars $) Pair Genotype $280.60 Homozygous for Npytm1Rpa x Homozygous for Npytm1Rpa
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| 002448 129S1/SvImJ | (approximate) | |
| 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. | ||
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