Description

Strain Information

Former Names C;129S-Vhlhtm1Jae/J    (Changed: 11-SEP-08 ) Type Mutant Stock; 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 ?+F20 (24-MAR-11) Generation Definitions   Donating Investigator Rudolf Jaenisch,   Whitehead Institute (MIT)

Description
This strain contains loxP sites flanking the Vhl promoter and exon 1 resulting in a conditional null allele. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Cre-mediated recombination results in the deletion of the promoter and exon 1. Studies in which liver-specific inactivation of the Vhl gene was achieved by breeding this strain with albumin promoter driven-Cre mice (see Stock No. 003574 for example) resulted in hemizygous mice that exhibit cavernous hemangiomas of the liver, a rare component of the human von Hippel-Lindau (VHL) disease. This strain represents an effective tool for generating tissue specific-targeted mutants useful in studies examining VHL and tumor suppression in general.

When bred to a strain expressing Cre recombinase in the myeloid cell lineage (see Stock No. 004781 for example), this mutant mouse strain may be useful in studies of myeloid cell mediated inflammation.

When bred to a strain expressing Cre recombinase in the kidney and genitourinary tract (see Stock No. 012237 for example), this mutant mouse strain may be useful in studies of genital pathologies associated with VHL disease.

Development
A vector containing Vhl exons 1-3 was used to construct the conditional allele. A positive-negative selection cassette, loxP-CMV-hyTK-loxP, was placed 2.6 Kb upstream of exon 1 and a loxP site positioned within intron 1. The targeting vector was electroporated into 129S4/SvJae-derived J1 embryonic stem cells which were subsequently transfected with a cytomegalovirus-driven Cre recombinase plasmid. ES cells in which Cre recombination resulted in exon 1 and the promoter being flanked by loxP sites (the 2-lox allele) were injected into BALB/c blastocysts.

Control Information

	Control
	None Available
Considerations for Choosing Controls

Related Strains

Strains carrying   Vhl^tm1Jae allele

012933

B6.129S4(C)-Vhltm1Jae/J

View Strains carrying   Vhl^tm1Jae     (1 strain)

Strains carrying other alleles of Vhl

003123	129S;ICR-Vhltm1Bjg/J
012933	B6.129S4(C)-Vhltm1Jae/J

View Strains carrying other alleles of Vhl     (2 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

Von Hippel-Lindau Syndrome; VHL - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Vhl^tm1Jae/Vhl^tm1Jae

        involves: 129S4/SvJae * BALB/c

• normal phenotype
• no abnormal phenotype detected   (MGI Ref ID J:67505)

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

Vhl^tm1Jae/Vhl^tm1Jae

        involves: 129S4/SvJae

• cellular phenotype
• decreased cell proliferation
  • of MEFs after 48 hours of culturing in normoxia or hypoxia conditions   (MGI Ref ID J:160941)

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Vhl^tm1Jae/Vhl^tm1Jae Lyz2^tm1(cre)Ifo/Lyz2⁺

        involves: 129P2/OlaHsd * 129S4/SvJae   (conditional)

• immune system phenotype
• increased inflammatory response
  • TPA-treated ears exhibit increased edema and inflammatory infiltration compared with similarly treated wild-type ears   (MGI Ref ID J:107682)

Vhl^tm1Jae/Vhl^tm1Jae Tg(Alb-cre)21Mgn/0

        involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA   (conditional)

• mortality/aging
• premature death
  • die between 6 and 13 weeks of age   (MGI Ref ID J:67505)
• growth/size phenotype
• decreased body weight
  • body weight is about 50% of wild-type   (MGI Ref ID J:67505)
• liver/biliary system phenotype
• abnormal liver morphology
  • numerous blood filled vascular cavities, but no large cavernous hemangiomas, are seen   (MGI Ref ID J:67505)
• • enlarged liver
    • severe   (MGI Ref ID J:67505)
  • hepatic steatosis
    • severe steatosis   (MGI Ref ID J:97652)
    • accumulation of neutral fats in hepatocytes is detectable by 2 weeks of age   (MGI Ref ID J:67505)
• cardiovascular system phenotype
• abnormal blood vessel morphology
  • foci of increased vascularization are present in the liver   (MGI Ref ID J:67505)
• • increased vascular endothelial cell number
    • proliferation of endothelial cells in hepatic blood vessels   (MGI Ref ID J:97652)
• abnormal vasodilation
  • hepatic vascular angiectasia   (MGI Ref ID J:97652)
• hematopoietic system phenotype
• polycythemia   (MGI Ref ID J:67505)
• muscle phenotype
• abnormal vasodilation
  • hepatic vascular angiectasia   (MGI Ref ID J:97652)

Vhl^tm1Jae/Vhl^tm1Jae Tg(Alb-cre)21Mgn/0

        involves: 129S4/SvJae * C57BL/6 * DBA   (conditional)

• mortality/aging
• premature death
  • mice die at 6 to 8 weeks of age   (MGI Ref ID J:144666)
• liver/biliary system phenotype
• abnormal liver morphology
  • at 6 weeks, the liver is friable and stippled with irregular yellow spots on a reddish black background unlike in wild-type mice   (MGI Ref ID J:144666)
  • hepatic vascularity is increased compared to in wild-type mice   (MGI Ref ID J:144666)
• • abnormal hepatocyte morphology
    • livers contain irregular, dilated, blood filled sinusoids and cytoplasmic vacuolizations within hepatocytes with eccentric nuclei unlike in wild-type mice   (MGI Ref ID J:144666)
  • hepatic steatosis
    • in a mixed micro- and macrovesicular steatotic pattern   (MGI Ref ID J:144666)
  • increased liver weight
    • at 6 weeks of age   (MGI Ref ID J:144666)
• increased hepatocyte proliferation   (MGI Ref ID J:144666)
• hematopoietic system phenotype
• increased hematocrit   (MGI Ref ID J:144666)
• reticulocytosis   (MGI Ref ID J:144666)
• cardiovascular system phenotype
• abnormal blood vessel morphology
  • hepatic vascularity is increased compared to in wild-type mice   (MGI Ref ID J:144666)
• growth/size phenotype
• decreased body size
  • mice are runted   (MGI Ref ID J:144666)
• integument phenotype
• reddish skin
  • of paws and unfurred skin by 4 to 6 weeks of age   (MGI Ref ID J:144666)
• cellular phenotype
• increased hepatocyte proliferation   (MGI Ref ID J:144666)

Vhl^tm1Jae/Vhl^tm1Jae Tg(Cdh16-cre)91Igr/0

        involves: 129S4/SvJae * ICR   (conditional)

• reproductive system phenotype
• abnormal epididymis morphology
  • aberrant presence of dilated blood capillaries surrounding epididymal tubules indicating increased vascularization   (MGI Ref ID J:137442)
  • however, the genital tracts of males and females look normal   (MGI Ref ID J:137442)

Vhl^tm1Jae/Vhl^tm1Jae Tg(Cdh16-cre)91Igr/0

        involves: 129S4/SvJae * BALB/c * C57BL/6J * ICR   (conditional)

• renal/urinary system phenotype
• hydronephrosis
  • hydronephrosis, characterized by an expansion of the renal pelvis   (MGI Ref ID J:137073)
  • however, mutants do not display histological abnormalities in the urothelium of the renal pelvis or ureter, or in the structure of the tubules in the kidney cortex or medulla   (MGI Ref ID J:137073)

View Research Applications

Research Applications

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

Research Tools
Cre-lox System
      loxP-flanked Sequences

Vhl^tm1Jae related

Cancer Research
Tumor Suppressor Genes

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Vhltm1Jae
Allele Name		targeted mutation 1, Rudolf Jaenisch
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		2-lox allele; VHL+f; VHL2; VHLf; Vhlh 2-lox; Vhlh+f; Vhlh2; Vhlh2lox; Vhlhfl;
Mutation Made By		Rudolf Jaenisch,   Massachusetts Institute of Technology
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Vhl, von Hippel-Lindau tumor suppressor
Chromosome		6
Gene Common Name(s)		HRCA1; RCA1; VHL1; Vhlh; pVHL; von Hippel-Lindau syndrome homolog;
Molecular Note		A CMV-hyTK selection cassette flanked by two loxP sites was inserted approximately 2.6 kb upstream of exon 1. A third loxP site was inserted into intron 1. The hygromycin cassette was deleted in ES cells by transient transfection with a vector driving expression of Cre recombinase. The resulting ES cell derivatives with two loxP sites flanking exon 1 were selected and injected into blastocysts to generate the Vhltm1Jae allele. [MGI Ref ID J:67505]

Genotyping

Genotyping Information

Genotyping Protocols

Vhl^tm1Jae, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Haase VH; Glickman JN; Socolovsky M; Jaenisch R. 2001. Vascular tumors in livers with targeted inactivation of the von Hippel-Lindau tumor suppressor. Proc Natl Acad Sci U S A 98(4):1583-8. [PubMed: 11171994]  [MGI Ref ID J:67505]

Additional References

Vhl^tm1Jae related

Biju MP; Neumann AK; Bensinger SJ; Johnson RS; Turka LA; Haase VH. 2004. Vhlh gene deletion induces hif-1-mediated cell death in thymocytes. Mol Cell Biol 24(20):9038-47. [PubMed: 15456877]  [MGI Ref ID J:93322]

Brukamp K; Jim B; Moeller MJ; Haase VH. 2007. Hypoxia and podocyte-specific Vhlh deletion confer risk of glomerular disease. Am J Physiol Renal Physiol 293(4):F1397-407. [PubMed: 17609290]  [MGI Ref ID J:143007]

Cantley J; Selman C; Shukla D; Abramov AY; Forstreuter F; Esteban MA; Claret M; Lingard SJ; Clements M; Harten SK; Asare-Anane H; Batterham RL; Herrera PL; Persaud SJ; Duchen MR; Maxwell PH; Withers DJ. 2009. Deletion of the von Hippel-Lindau gene in pancreatic beta cells impairs glucose homeostasis in mice. J Clin Invest 119(1):125-35. [PubMed: 19065050]  [MGI Ref ID J:144713]

Chan SY; Zhang YY; Hemann C; Mahoney CE; Zweier JL; Loscalzo J. 2009. MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2. Cell Metab 10(4):273-84. [PubMed: 19808020]  [MGI Ref ID J:153662]

Choi D; Cai EP; Schroer SA; Wang L; Woo M. 2011. Vhl is required for normal pancreatic beta cell function and the maintenance of beta cell mass with age in mice. Lab Invest 91(4):527-38. [PubMed: 21242957]  [MGI Ref ID J:170625]

Cramer T; Yamanishi Y; Clausen BE; Forster I; Pawlinski R; Mackman N; Haase VH; Jaenisch R; Corr M; Nizet V; Firestein GS; Gerber HP; Ferrara N; Johnson RS. 2003. HIF-1alpha is essential for myeloid cell-mediated inflammation. Cell 112(5):645-57. [PubMed: 12628185]  [MGI Ref ID J:107682]

Ding M; Cui S; Li C; Jothy S; Haase V; Steer BM; Marsden PA; Pippin J; Shankland S; Rastaldi MP; Cohen CD; Kretzler M; Quaggin SE. 2006. Loss of the tumor suppressor Vhlh leads to upregulation of Cxcr4 and rapidly progressive glomerulonephritis in mice. Nat Med 12(9):1081-7. [PubMed: 16906157]  [MGI Ref ID J:115017]

Frew IJ; Minola A; Georgiev S; Hitz M; Moch H; Richard S; Vortmeyer AO; Krek W. 2008. Combined VHLH and PTEN mutation causes genital tract cystadenoma and squamous metaplasia. Mol Cell Biol 28(14):4536-48. [PubMed: 18474617]  [MGI Ref ID J:137442]

Frew IJ; Thoma CR; Georgiev S; Minola A; Hitz M; Montani M; Moch H; Krek W. 2008. pVHL and PTEN tumour suppressor proteins cooperatively suppress kidney cyst formation. EMBO J 27(12):1747-57. [PubMed: 18497742]  [MGI Ref ID J:137073]

Haase VH. 2005. The VHL tumor suppressor in development and disease: functional studies in mice by conditional gene targeting. Semin Cell Dev Biol 16(4-5):564-74. [PubMed: 15908240]  [MGI Ref ID J:101112]

Hsouna A; Nallamothu G; Kose N; Guinea M; Dammai V; Hsu T. 2010. Drosophila von Hippel-Lindau tumor suppressor gene function in epithelial tubule morphogenesis. Mol Cell Biol 30(15):3779-94. [PubMed: 20516215]  [MGI Ref ID J:162786]

Kapitsinou PP; Liu Q; Unger TL; Rha J; Davidoff O; Keith B; Epstein JA; Moores SL; Erickson-Miller CL; Haase VH. 2010. Hepatic HIF-2 regulates erythropoietic responses to hypoxia in renal anemia. Blood 116(16):3039-48. [PubMed: 20628150]  [MGI Ref ID J:165868]

Karhausen J; Furuta GT; Tomaszewski JE; Johnson RS; Colgan SP; Haase VH. 2004. Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. J Clin Invest 114(8):1098-106. [PubMed: 15489957]  [MGI Ref ID J:93476]

Kim WY; Safran M; Buckley MR; Ebert BL; Glickman J; Bosenberg M; Regan M; Kaelin WG Jr. 2006. Failure to prolyl hydroxylate hypoxia-inducible factor alpha phenocopies VHL inactivation in vivo. EMBO J 25(19):4650-62. [PubMed: 16977322]  [MGI Ref ID J:144666]

Kimura K; Iwano M; Higgins DF; Yamaguchi Y; Nakatani K; Harada K; Kubo A; Akai Y; Rankin EB; Neilson EG; Haase VH; Saito Y. 2008. Stable expression of HIF-1alpha in tubular epithelial cells promotes interstitial fibrosis. Am J Physiol Renal Physiol 295(4):F1023-9. [PubMed: 18667485]  [MGI Ref ID J:153791]

Krishnan J; Suter M; Windak R; Krebs T; Felley A; Montessuit C; Tokarska-Schlattner M; Aasum E; Bogdanova A; Perriard E; Perriard JC; Larsen T; Pedrazzini T; Krek W. 2009. Activation of a HIF1alpha-PPARgamma axis underlies the integration of glycolytic and lipid anabolic pathways in pathologic cardiac hypertrophy. Cell Metab 9(6):512-24. [PubMed: 19490906]  [MGI Ref ID J:149827]

Kurihara T; Kubota Y; Ozawa Y; Takubo K; Noda K; Simon MC; Johnson RS; Suematsu M; Tsubota K; Ishida S; Goda N; Suda T; Okano H. 2010. von Hippel-Lindau protein regulates transition from the fetal to the adult circulatory system in retina. Development 137(9):1563-71. [PubMed: 20388654]  [MGI Ref ID J:160163]

Kurihara T; Westenskow PD; Krohne TU; Aguilar E; Johnson RS; Friedlander M. 2011. Astrocyte pVHL and HIF-alpha isoforms are required for embryonic-to-adult vascular transition in the eye. J Cell Biol 195(4):689-701. [PubMed: 22084310]  [MGI Ref ID J:178823]

Lei L; Mason S; Liu D; Huang Y; Marks C; Hickey R; Jovin IS; Pypaert M; Johnson RS; Giordano FJ. 2008. Hypoxia-inducible factor-dependent degeneration, failure, and malignant transformation of the heart in the absence of the von Hippel-Lindau protein. Mol Cell Biol 28(11):3790-803. [PubMed: 18285456]  [MGI Ref ID J:136012]

Liu Y; Pop R; Sadegh C; Brugnara C; Haase VH; Socolovsky M. 2006. Suppression of Fas-FasL coexpression by erythropoietin mediates erythroblast expansion during the erythropoietic stress response in vivo. Blood 108(1):123-33. [PubMed: 16527892]  [MGI Ref ID J:135682]

Minamishima YA; Kaelin WG Jr. 2010. Reactivation of hepatic EPO synthesis in mice after PHD loss. Science 329(5990):407. [PubMed: 20651146]  [MGI Ref ID J:162614]

Minamishima YA; Moslehi J; Bardeesy N; Cullen D; Bronson RT; Kaelin WG Jr. 2008. Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure. Blood 111(6):3236-44. [PubMed: 18096761]  [MGI Ref ID J:132718]

Minamishima YA; Moslehi J; Padera RF; Bronson RT; Liao R; Kaelin WG Jr. 2009. A feedback loop involving the Phd3 prolyl hydroxylase tunes the mammalian hypoxic response in vivo. Mol Cell Biol 29(21):5729-41. [PubMed: 19720742]  [MGI Ref ID J:153985]

Miro-Murillo M; Elorza A; Soro-Arnaiz I; Albacete-Albacete L; Ordonez A; Balsa E; Vara-Vega A; Vazquez S; Fuertes E; Fernandez-Criado C; Landazuri MO; Aragones J. 2011. Acute Vhl Gene Inactivation Induces Cardiac HIF-Dependent Erythropoietin Gene Expression. PLoS One 6(7):e22589. [PubMed: 21811636]  [MGI Ref ID J:174924]

Moslehi J; Minamishima YA; Shi J; Neuberg D; Charytan DM; Padera RF; Signoretti S; Liao R; Kaelin WG Jr. 2010. Loss of hypoxia-inducible factor prolyl hydroxylase activity in cardiomyocytes phenocopies ischemic cardiomyopathy. Circulation 122(10):1004-16. [PubMed: 20733101]  [MGI Ref ID J:179490]

Neumann AK; Yang J; Biju MP; Joseph SK; Johnson RS; Haase VH; Freedman BD; Turka LA. 2005. Hypoxia inducible factor 1 alpha regulates T cell receptor signal transduction. Proc Natl Acad Sci U S A 102(47):17071-6. [PubMed: 16286658]  [MGI Ref ID J:103837]

Park SK; Haase VH; Johnson RS. 2007. von Hippel Lindau tumor suppressor regulates hepatic glucose metabolism by controlling expression of glucose transporter 2 and glucose 6-phosphatase. Int J Oncol 30(2):341-8. [PubMed: 17203215]  [MGI Ref ID J:123030]

Peyssonnaux C; Datta V; Cramer T; Doedens A; Theodorakis EA; Gallo RL; Hurtado-Ziola N; Nizet V; Johnson RS. 2005. HIF-1alpha expression regulates the bactericidal capacity of phagocytes. J Clin Invest 115(7):1806-15. [PubMed: 16007254]  [MGI Ref ID J:99628]

Peyssonnaux C; Zinkernagel AS; Schuepbach RA; Rankin E; Vaulont S; Haase VH; Nizet V; Johnson RS. 2007. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J Clin Invest 117(7):1926-32. [PubMed: 17557118]  [MGI Ref ID J:124039]

Pfander D; Kobayashi T; Knight MC; Zelzer E; Chan DA; Olsen BR; Giaccia AJ; Johnson RS; Haase VH; Schipani E. 2004. Deletion of Vhlh in chondrocytes reduces cell proliferation and increases matrix deposition during growth plate development. Development 131(10):2497-508. [PubMed: 15128677]  [MGI Ref ID J:91056]

Puri S; Cano DA; Hebrok M. 2009. A role for von Hippel-Lindau protein in pancreatic beta-cell function. Diabetes 58(2):433-41. [PubMed: 19033400]  [MGI Ref ID J:146940]

Rankin EB; Biju MP; Liu Q; Unger TL; Rha J; Johnson RS; Simon MC; Keith B; Haase VH. 2007. Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo. J Clin Invest 117(4):1068-77. [PubMed: 17404621]  [MGI Ref ID J:121253]

Rankin EB; Higgins DF; Walisser JA; Johnson RS; Bradfield CA; Haase VH. 2005. Inactivation of the arylhydrocarbon receptor nuclear translocator (Arnt) suppresses von Hippel-Lindau disease-associated vascular tumors in mice. Mol Cell Biol 25(8):3163-72. [PubMed: 15798202]  [MGI Ref ID J:97652]

Rankin EB; Rha J; Selak MA; Unger TL; Keith B; Liu Q; Haase VH. 2009. Hypoxia-inducible factor 2 regulates hepatic lipid metabolism. Mol Cell Biol 29(16):4527-38. [PubMed: 19528226]  [MGI Ref ID J:151523]

Rankin EB; Rha J; Unger TL; Wu CH; Shutt HP; Johnson RS; Simon MC; Keith B; Haase VH. 2008. Hypoxia-inducible factor-2 regulates vascular tumorigenesis in mice. Oncogene 27(40):5354-8. [PubMed: 18490920]  [MGI Ref ID J:140075]

Rankin EB; Tomaszewski JE; Haase VH. 2006. Renal cyst development in mice with conditional inactivation of the von Hippel-Lindau tumor suppressor. Cancer Res 66(5):2576-83. [PubMed: 16510575]  [MGI Ref ID J:106705]

Seagroves TN; Peacock DL; Liao D; Schwab LP; Krueger R; Handorf CR; Haase VH; Johnson RS. 2010. VHL deletion impairs mammary alveologenesis but is not sufficient for mammary tumorigenesis. Am J Pathol 176(5):2269-82. [PubMed: 20382704]  [MGI Ref ID J:160375]

Shah YM; Ito S; Morimura K; Chen C; Yim SH; Haase VH; Gonzalez FJ. 2008. Hypoxia-inducible factor augments experimental colitis through an MIF-dependent inflammatory signaling cascade. Gastroenterology 134(7):2036-48, 2048.e1-3. [PubMed: 18439915]  [MGI Ref ID J:136664]

Shah YM; Matsubara T; Ito S; Yim SH; Gonzalez FJ. 2009. Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency. Cell Metab 9(2):152-64. [PubMed: 19147412]  [MGI Ref ID J:145975]

Steenhard BM; Isom K; Stroganova L; St John PL; Zelenchuk A; Freeburg PB; Holzman LB; Abrahamson DR. 2010. Deletion of von Hippel-Lindau in glomerular podocytes results in glomerular basement membrane thickening, ectopic subepithelial deposition of collagen {alpha}1{alpha}2{alpha}1(IV), expression of neuroglobin, and proteinuria. Am J Pathol 177(1):84-96. [PubMed: 20522651]  [MGI Ref ID J:162099]

Takubo K; Goda N; Yamada W; Iriuchishima H; Ikeda E; Kubota Y; Shima H; Johnson RS; Hirao A; Suematsu M; Suda T. 2010. Regulation of the HIF-1alpha level is essential for hematopoietic stem cells. Cell Stem Cell 7(3):391-402. [PubMed: 20804974]  [MGI Ref ID J:164436]

Tang N; Mack F; Haase VH; Simon MC; Johnson RS. 2006. pVHL function is essential for endothelial extracellular matrix deposition. Mol Cell Biol 26(7):2519-30. [PubMed: 16537898]  [MGI Ref ID J:106926]

Theilig F; Enke AK; Scolari B; Polzin D; Bachmann S; Koesters R. 2011. Tubular Deficiency of von Hippel-Lindau Attenuates Renal Disease Progression in Anti-GBM Glomerulonephritis. Am J Pathol 179(5):2177-88. [PubMed: 21925138]  [MGI Ref ID J:177371]

Thorner PS; Ho M; Eremina V; Sado Y; Quaggin S. 2008. Podocytes contribute to the formation of glomerular crescents. J Am Soc Nephrol 19(3):495-502. [PubMed: 18199804]  [MGI Ref ID J:150172]

Wan C; Gilbert SR; Wang Y; Cao X; Shen X; Ramaswamy G; Jacobsen KA; Alaql ZS; Eberhardt AW; Gerstenfeld LC; Einhorn TA; Deng L; Clemens TL. 2008. Activation of the hypoxia-inducible factor-1alpha pathway accelerates bone regeneration. Proc Natl Acad Sci U S A 105(2):686-91. [PubMed: 18184809]  [MGI Ref ID J:131088]

Wang Y; Wan C; Deng L; Liu X; Cao X; Gilbert SR; Bouxsein ML; Faugere MC; Guldberg RE; Gerstenfeld LC; Haase VH; Johnson RS; Schipani E; Clemens TL. 2007. The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest 117(6):1616-26. [PubMed: 17549257]  [MGI Ref ID J:122021]

Weidemann A; Kerdiles YM; Knaup KX; Rafie CA; Boutin AT; Stockmann C; Takeda N; Scadeng M; Shih AY; Haase VH; Simon MC; Kleinfeld D; Johnson RS. 2009. The glial cell response is an essential component of hypoxia-induced erythropoiesis in mice. J Clin Invest 119(11):3373-83. [PubMed: 19809162]  [MGI Ref ID J:154613]

Weidemann A; Krohne TU; Aguilar E; Kurihara T; Takeda N; Dorrell MI; Simon MC; Haase VH; Friedlander M; Johnson RS. 2010. Astrocyte hypoxic response is essential for pathological but not developmental angiogenesis of the retina. Glia 58(10):1177-85. [PubMed: 20544853]  [MGI Ref ID J:168049]

Welford SM; Dorie MJ; Li X; Haase VH; Giaccia AJ. 2010. Renal oxygenation suppresses VHL loss-induced senescence that is caused by increased sensitivity to oxidative stress. Mol Cell Biol 30(19):4595-603. [PubMed: 20679489]  [MGI Ref ID J:164903]

Young AP; Schlisio S; Minamishima YA; Zhang Q; Li L; Grisanzio C; Signoretti S; Kaelin WG Jr. 2008. VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400. Nat Cell Biol 10(3):361-9. [PubMed: 18297059]  [MGI Ref ID J:145670]

Zehetner J; Danzer C; Collins S; Eckhardt K; Gerber PA; Ballschmieter P; Galvanovskis J; Shimomura K; Ashcroft FM; Thorens B; Rorsman P; Krek W. 2008. pVHL is a regulator of glucose metabolism and insulin secretion in pancreatic {beta} cells. Genes Dev 22(22):3135-46. [PubMed: 19056893]  [MGI Ref ID J:142036]

Zhang N; Fu Z; Linke S; Chicher J; Gorman JJ; Visk D; Haddad GG; Poellinger L; Peet DJ; Powell F; Johnson RS. 2010. The asparaginyl hydroxylase factor inhibiting HIF-1alpha is an essential regulator of metabolism. Cell Metab 11(5):364-78. [PubMed: 20399150]  [MGI Ref ID J:160941]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	This strain originated and is maintained on a C;129S background. It is maintained as a homozygote. Coat color expected from breeding:Albino, Agouti
Mating System	Homozygote x Homozygote         (Female x Male)   01-MAR-06
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	None Available
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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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
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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, 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.

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.