|Please refer to the Mutant Mouse Regional Resource Center (MMRRC) for information about B6;129S4-Ptpn1tm2Bbk/Mmjax MMRRC Stock Number 032243.|
|These mutant mice possess loxP sites flanking introns 5 to 8 of the protein tyrosine phosphatase, non-receptor type 1 (Ptpn1) gene and may be useful for studying energy regulation, adiposity, glucose homeostatsis and leptin sensitivity.|
Type Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N?F?pN1
Donating Investigator Benjamin Neel, Ontario Cancer Institute
Mice homozygous for the targeted mutation are viable and fertile. Homozygous mutant mice show no overt phenotypic abnormalities. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific mutants of the floxed allele. This mutant mouse strain may be useful in generating conditional mutations to study energy regulation, adiposity, glucose homeostatsis and leptin sensitivity.
For example, when bred to mice carrying Tg(Alb-cre)21Mgn,Cre recombinase expression is directed to the liver; this mutant mouse strain may be useful in studies of body weight regulation.
When bred to mice carrying Tg(Nes-cre)1Kln, Cre recombinase is directed to the central and peripheral nervous system; this mutant mouse strain may be useful in studies of the regulation of adiposity, leptin and body weight.
A targeting vector was designed to place a loxP -flanked PGKneo cassette in intron 5 and a loxP site in intron 8 encompassing the protein active site and parts of the catalytic domain. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The neomycin cassette was removed by transient transfection with a Cre recombinase expressing plasmid leaving loxP sites in introns 5 and 8. The resulting chimeric animals were crossed to C57BL/6J and then intercrossed. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
|Considerations for Choosing Controls|
Strains carrying other alleles of Ptpn1
012677 B6.129S4-Ptpn1tm1Bbk/Mmjax 012678 FVB.129S4(B6)-Ptpn1tm1Bbk/MmjaxView Strains carrying other alleles of Ptpn1 (2 strains)
View Related Disease (OMIM) TermsRelated Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.View Mammalian Phenotype TermsMammalian Phenotype Terms provided by MGIassigned by genotype
The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services firstname.lastname@example.org for customized breeding options.
Ptpn1tm2Bbk/Ptpn1tm2Bbk Tg(Alb-cre)21Mgn/0involves: 129S4/SvJae * C57BL/6 * DBA/2 (conditional)
- growth/size/body phenotype
- *normal* growth/size/body phenotype
- mice with liver-specific Ptpn1 deletion show similar body weight to Ptpn1-sufficient controls (MGI Ref ID J:111969)
Ptpn1tm2Bbk/Ptpn1tm2Bbk Tg(Nes-cre)1Kln/0involves: 129S4/SvJae * C57BL/6 * SJL (conditional)
- growth/size/body phenotype
- decreased body weight
- male neuronal Ptpn1-deficient mice show significantly reduced body weight on a high fat diet compared to control Ptpn1-sufficient (undeleted Ptpn1tm2Bbk homozygous) animals between 9 and 17 weeks of age; females show reduced body weight but less markedly so than control female mice on a high fat diet (MGI Ref ID J:111969)
- neuronal Ptpn1-deficient mice also weigh less than controls when fed a regular chow diet (decrease of 4.5% fat by weight) (MGI Ref ID J:111969)
- decreased susceptibility to diet-induced obesity
- when fed a high-fat diet (MGI Ref ID J:179621)
- homeostasis/metabolism phenotype
- abnormal homeostasis
- whether fed standard chow or a high-fat diet, leptin-treated mice exhibit enhanced leptin sensitivity compared with wild-type mice (MGI Ref ID J:179621)
- abnormal hormone level
- leptin protein is elevated in white adipose tissue of these mice, suggesting that increased serum leptin levels are due to increased adipocyte leptin production (MGI Ref ID J:111969)
- decreased circulating insulin level
- mutants have lower seurm insulin levels on regular chow and HFD vs controls (MGI Ref ID J:111969)
- decreased circulating leptin level (MGI Ref ID J:179621)
- increased adiponectin level
- adiponectin levels are elevated and resistin levels are unexpectedly normal in mutants on regular and HFD diets (MGI Ref ID J:111969)
- increased circulating leptin level
- neuronal Ptpn1-deficient mice show increased serum leptin levels (2.3 -fold on a regular chow diet, 4.4-fold higher on a HFD) compared to Ptpn1-undeleted littermates, detected 4 weeks after birth (MGI Ref ID J:111969)
- decreased circulating glucose level
- mutants have lower fed blood glucose on regular chow and HFD vs controls (MGI Ref ID J:111969)
- decreased respiratory quotient
- mice display greater oxygen consumption and a decreased respiratory quotient (MGI Ref ID J:111969)
- decreased susceptibility to diet-induced obesity
- when fed a high-fat diet (MGI Ref ID J:179621)
- decreased triglyceride level
- mice show reduced adiposity after high-fat feeding based on lower carcass triglyceride content compared to controls (MGI Ref ID J:111969)
- improved glucose tolerance
- male mice at 8-10 weeks of age show enhanced glucose tolerance compared to littermate comtrols (MGI Ref ID J:111969)
- increased insulin sensitivity (MGI Ref ID J:179621)
- male mice at 8-10 weeks of age show improved insulin sensitivity compared to littermate controls (MGI Ref ID J:111969)
- female mice also show significantly improved insulin sensitivity even though weight at 8 weeks of age is the same as controls; insulin sensitivity and glucose tolerance are similar to whole body deficient Ptpn1tm1Bbk mice (MGI Ref ID J:111969)
- increased oxygen consumption (MGI Ref ID J:111969)
- behavior/neurological phenotype
- abnormal food intake
- decreased food intake
- male mice injected with leptin show decreased food intake during the period of treatment compared to controls (MGI Ref ID J:111969)
- abnormal motor capabilities/coordination/movement
- neuronal Ptpn1-deficient mice display increased ambulatory movement vs control (MGI Ref ID J:111969)
- skeleton phenotype
- decreased bone mineral density
- when treated with leptin twice per day over a 60 hour period, male mice show reduced bone mineral density (MGI Ref ID J:111969)
- adipose tissue phenotype
- abnormal fat pad morphology (MGI Ref ID J:111969)
View Research ApplicationsResearch ApplicationsThis mouse can be used to support research in many areas including:
Diabetes and Obesity Research
|Allele Name||targeted mutation 2, Barbara B Kahn|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Common Name(s)||PTP-1Bfl; Ptpnflox;|
|Mutation Made By||Benjamin Neel, Ontario Cancer Institute|
|Strain of Origin||129S4/SvJae|
|Gene Symbol and Name||Ptpn1, protein tyrosine phosphatase, non-receptor type 1|
|Gene Common Name(s)||PTP-1B; PTP1B; Ptp;|
|Molecular Note||A targeting vector was designed to flank exons 6-8 of the locus. This sequence encompasses the active site and surrounding parts of the catalytic domain. A floxed neo was removed via cre mediated excision. [MGI Ref ID J:111969]|
Bence KK; Delibegovic M; Xue B; Gorgun CZ; Hotamisligil GS; Neel BG; Kahn BB. 2006. Neuronal PTP1B regulates body weight, adiposity and leptin action. Nat Med 12(8):917-24. [PubMed: 16845389] [MGI Ref ID J:111969]
Agouni A; Mody N; Owen C; Czopek A; Zimmer D; Bentires-Alj M; Bence KK; Delibegovic M. 2011. Liver-specific deletion of protein tyrosine phosphatase (PTP) 1B improves obesity- and pharmacologically induced endoplasmic reticulum stress. Biochem J 438(2):369-78. [PubMed: 21605081] [MGI Ref ID J:177894]
Balavenkatraman KK; Aceto N; Britschgi A; Mueller U; Bence KK; Neel BG; Bentires-Alj M. 2011. Epithelial protein-tyrosine phosphatase 1B contributes to the induction of mammary tumors by HER2/Neu but is not essential for tumor maintenance. Mol Cancer Res 9(10):1377-84. [PubMed: 21849469] [MGI Ref ID J:205401]
Banno R; Zimmer D; De Jonghe BC; Atienza M; Rak K; Yang W; Bence KK. 2010. PTP1B and SHP2 in POMC neurons reciprocally regulate energy balance in mice. J Clin Invest 120(3):720-34. [PubMed: 20160350] [MGI Ref ID J:158568]
Basavarajappa DK; Gupta VK; Dighe R; Rajala A; Rajala RV. 2011. Phosphorylated Grb14 Is an Endogenous Inhibitor of Retinal Protein Tyrosine Phosphatase 1B, and Light-Dependent Activation of Src Phosphorylates Grb14. Mol Cell Biol 31(19):3975-87. [PubMed: 21791607] [MGI Ref ID J:175867]
Berdnikovs S; Abdala-Valencia H; Cook-Mills JM. 2013. Endothelial cell PTP1B regulates leukocyte recruitment during allergic inflammation. Am J Physiol Lung Cell Mol Physiol 304(4):L240-9. [PubMed: 23275627] [MGI Ref ID J:194934]
Briancon N; McNay DE; Maratos-Flier E; Flier JS. 2010. Combined neural inactivation of suppressor of cytokine signaling-3 and protein-tyrosine phosphatase-1B reveals additive, synergistic, and factor-specific roles in the regulation of body energy balance. Diabetes 59(12):3074-84. [PubMed: 20876718] [MGI Ref ID J:169330]
Chiappini F; Catalano KJ; Lee J; Peroni OD; Lynch J; Dhaneshwar AS; Wellenstein K; Sontheimer A; Neel BG; Kahn BB. 2014. Ventromedial hypothalamus-specific Ptpn1 deletion exacerbates diet-induced obesity in female mice. J Clin Invest 124(9):3781-92. [PubMed: 25083988] [MGI Ref ID J:215768]
De Jonghe BC; Hayes MR; Banno R; Skibicka KP; Zimmer DJ; Bowen KA; Leichner TM; Alhadeff AL; Kanoski SE; Cyr NE; Nillni EA; Grill HJ; Bence KK. 2011. Deficiency of PTP1B in POMC neurons leads to alterations in energy balance and homeostatic response to cold exposure. Am J Physiol Endocrinol Metab 300(6):E1002-11. [PubMed: 21406615] [MGI Ref ID J:172299]
De Jonghe BC; Hayes MR; Zimmer DJ; Kanoski SE; Grill HJ; Bence KK. 2012. Food intake reductions and increases in energetic responses by hindbrain leptin and melanotan II are enhanced in mice with POMC-specific PTP1B deficiency. Am J Physiol Endocrinol Metab 303(5):E644-51. [PubMed: 22761160] [MGI Ref ID J:189527]
Delibegovic M; Bence KK; Mody N; Hong EG; Ko HJ; Kim JK; Kahn BB; Neel BG. 2007. Improved glucose homeostasis in mice with muscle-specific deletion of protein-tyrosine phosphatase 1B. Mol Cell Biol 27(21):7727-34. [PubMed: 17724080] [MGI Ref ID J:129081]
Delibegovic M; Zimmer D; Kauffman C; Rak K; Hong EG; Cho YR; Kim JK; Kahn BB; Neel BG; Bence KK. 2009. Liver-specific deletion of protein-tyrosine phosphatase 1B (PTP1B) improves metabolic syndrome and attenuates diet-induced endoplasmic reticulum stress. Diabetes 58(3):590-9. [PubMed: 19074988] [MGI Ref ID J:146928]
Dodd GT; Decherf S; Loh K; Simonds SE; Wiede F; Balland E; Merry TL; Munzberg H; Zhang ZY; Kahn BB; Neel BG; Bence KK; Andrews ZB; Cowley MA; Tiganis T. 2015. Leptin and insulin act on POMC neurons to promote the browning of white fat. Cell 160(1-2):88-104. [PubMed: 25594176] [MGI Ref ID J:219581]
Fuentes F; Zimmer D; Atienza M; Schottenfeld J; Penkala I; Bale T; Bence KK; Arregui CO. 2012. Protein tyrosine phosphatase PTP1B is involved in hippocampal synapse formation and learning. PLoS One 7(7):e41536. [PubMed: 22844492] [MGI Ref ID J:189720]
Grant L; Shearer KD; Czopek A; Lees EK; Owen C; Agouni A; Workman J; Martin-Granados C; Forrester JV; Wilson HM; Mody N; Delibegovic M. 2014. Myeloid-cell protein tyrosine phosphatase-1B deficiency in mice protects against high-fat diet and lipopolysaccharide-induced inflammation, hyperinsulinemia, and endotoxemia through an IL-10 STAT3-dependent mechanism. Diabetes 63(2):456-70. [PubMed: 24186864] [MGI Ref ID J:209005]
Kumagai T; Baldwin C; Aoudjit L; Nezvitsky L; Robins R; Jiang R; Takano T. 2014. Protein tyrosine phosphatase 1B inhibition protects against podocyte injury and proteinuria. Am J Pathol 184(8):2211-24. [PubMed: 24951831] [MGI Ref ID J:213558]
Lackey DE; Lynch CJ; Olson KC; Mostaedi R; Ali M; Smith WH; Karpe F; Humphreys S; Bedinger DH; Dunn TN; Thomas AP; Oort PJ; Kieffer DA; Amin R; Bettaieb A; Haj FG; Permana P; Anthony TG; Adams SH. 2013. Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity. Am J Physiol Endocrinol Metab 304(11):E1175-87. [PubMed: 23512805] [MGI Ref ID J:198119]
Lee KY; Russell SJ; Ussar S; Boucher J; Vernochet C; Mori MA; Smyth G; Rourk M; Cederquist C; Rosen ED; Kahn BB; Kahn CR. 2013. Lessons on conditional gene targeting in mouse adipose tissue. Diabetes 62(3):864-74. [PubMed: 23321074] [MGI Ref ID J:198116]
Liu S; Xi Y; Bettaieb A; Matsuo K; Matsuo I; Kulkarni RN; Haj FG. 2014. Disruption of protein-tyrosine phosphatase 1B expression in the pancreas affects beta-cell function. Endocrinology 155(9):3329-38. [PubMed: 24956127] [MGI Ref ID J:217005]
Loh K; Fukushima A; Zhang X; Galic S; Briggs D; Enriori PJ; Simonds S; Wiede F; Reichenbach A; Hauser C; Sims NA; Bence KK; Zhang S; Zhang ZY; Kahn BB; Neel BG; Andrews ZB; Cowley MA; Tiganis T. 2011. Elevated hypothalamic TCPTP in obesity contributes to cellular leptin resistance. Cell Metab 14(5):684-99. [PubMed: 22000926] [MGI Ref ID J:179621]
Medgyesi D; Hobeika E; Biesen R; Kollert F; Taddeo A; Voll RE; Hiepe F; Reth M. 2014. The protein tyrosine phosphatase PTP1B is a negative regulator of CD40 and BAFF-R signaling and controls B cell autoimmunity. J Exp Med 211(3):427-40. [PubMed: 24590766] [MGI Ref ID J:210736]
Owen C; Lees EK; Grant L; Zimmer DJ; Mody N; Bence KK; Delibegovic M. 2013. Inducible liver-specific knockdown of protein tyrosine phosphatase 1B improves glucose and lipid homeostasis in adult mice. Diabetologia 56(10):2286-96. [PubMed: 23832083] [MGI Ref ID J:203304]
Ozek C; Kanoski SE; Zhang ZY; Grill HJ; Bence KK. 2014. Protein-tyrosine phosphatase 1B (PTP1B) is a novel regulator of central brain-derived neurotrophic factor and tropomyosin receptor kinase B (TrkB) signaling. J Biol Chem 289(46):31682-92. [PubMed: 25288805] [MGI Ref ID J:218302]
Rajala RV; Tanito M; Neel BG; Rajala A. 2010. Enhanced retinal insulin receptor-activated neuroprotective survival signal in mice lacking the protein-tyrosine phosphatase-1B gene. J Biol Chem 285(12):8894-904. [PubMed: 20061388] [MGI Ref ID J:161083]
Tsou RC; Rak KS; Zimmer DJ; Bence KK. 2014. Improved metabolic phenotype of hypothalamic PTP1B-deficiency is dependent upon the leptin receptor. Mol Metab 3(3):301-12. [PubMed: 24749060] [MGI Ref ID J:208832]
Tsou RC; Zimmer DJ; De Jonghe BC; Bence KK. 2012. Deficiency of PTP1B in leptin receptor-expressing neurons leads to decreased body weight and adiposity in mice. Endocrinology 153(9):4227-37. [PubMed: 22802463] [MGI Ref ID J:189156]
Xue B; Pulinilkunnil T; Murano I; Bence KK; He H; Minokoshi Y; Asakura K; Lee A; Haj F; Furukawa N; Catalano KJ; Delibegovic M; Balschi JA; Cinti S; Neel BG; Kahn BB. 2009. Neuronal protein tyrosine phosphatase 1B deficiency results in inhibition of hypothalamic AMPK and isoform-specific activation of AMPK in peripheral tissues. Mol Cell Biol 29(16):4563-73. [PubMed: 19528236] [MGI Ref ID J:151519]
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Breeding & Husbandry While maintaining a live colony, these mice are bred as homozygotes.
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