Description

Strain Information

Former Names STOCK Cavtm1Mls/J    (Changed: 21-DEC-04 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation F?+12 (21-JAN-08)   Donating Investigator Michael Lisanti,   The Albert Einstein College of Medicine

Description
Mice that are homozygous for the targeted mutation are viable, fertile and do not display any gross physical abnormalities. Mutant mice exhibit exercise intolerance when challenged and are slightly hyperphagic. No gene product (protein) is detected by Western blot analysis in adipose, lung and heart tissues or in cultured mouse embryonic fibroblasts (MEFs). A decrease in the level of co-expressed caveolin-2 protein is immunodetected. At age 4-5 months, mutant mice are often smaller than their wildtype littermates. By one year of age, mutant mice weigh 5 to 7 grams less than wildtype, and are resistant to diet-induced obesity. Progressive adipose pathology results in reduced white adipose tissue with abnormally small adipocytes and enlarged, hyperplastic brown adipose tissue. Homozygotes display lipid metabolism and uptake disruption with elevated serum triglycerides and free fatty acid levels, and reduced leptin levels. Isolated aortic tissue segments have a diminished vasoconstriction response to the alpha-1-adrenergic receptor agonist, phenylephrine, and an enhanced vasorelaxation response to acetylcholine. Histological examination of lung tissue from mutant mice shows thickened alveolar septa, hypercellularity, reduced alveolar spaces and increased density of basement membranes and reticulin fibers. Furtherimmunohistochemical examination of lung tissue shows an increased number of endothelial cells. Mutant derived MEF cells proliferate two times faster and are denser at confluence as indicated by growth curves and cell cycle analysis. Electron microscopy analysis reveals a complete absence of caveolae (plasmalemmal vesicles) in endothelial cells. In vitro studies measuring uptake of fluorescently-labeled albumin and in vivo studies following uptake of gold-conjugated albumin demonstrate caveolar endocytosis impairment. This mutant mouse strain may be useful in studies of vesicular and cholesterol trafficking, signal transduction and tumor suppression.

Development
A targeting vector containing a neomycin resistance gene was used to disrupt 2.2 Kb of sequence containing exons 1 and 2. The construct was electroporated into WW6 embryonic stem (ES) cells(75% 129/Sv, 20% C57BL/6J, 5% SJL). Correctly targeted ES cells were injected into C57BL/6 blastocysts.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Cav1^tm1Mls allele

007083

B6.Cg-Cav1tm1Mls/J

View Strains carrying   Cav1^tm1Mls     (1 strain)

Additional Web Information

Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Cav1^tm1Mls/Cav1^tm1Mls

        involves: 129/Sv * C57BL/6 * SJL

• cardiovascular system phenotype
• abnormal vasoconstriction (MGI Ref ID J:75193)
  • impaired response to phenylephrine (PE) due to increased Nos3 activity
• abnormal vasodilation (MGI Ref ID J:75193)
  • impaired acetylcholine induced relaxation of the aortic rings
• cellular phenotype
• absent caveolae (MGI Ref ID J:75193)
  • endothelial cells lack caveolae membranes
• respiratory system phenotype
• abnormal lung morphology (MGI Ref ID J:75193)
  • parenchymal hypercellularity
• thick alveolar septum (MGI Ref ID J:75193)
• homeostasis/metabolism phenotype
• abnormal exercise endurance (MGI Ref ID J:75193)
  • exercise intolerance when compared to wild-type in a swimming test

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

Cav1^tm1Mls/Cav1^tm1Mls

        involves: 129/Sv * C57BL/6

• adipose tissue phenotype
• abnormal adipocyte morphology (MGI Ref ID J:75192)
  • at 12 weeks of age, female mammary gland 4/subcutaneous adipocytes contain reduced lipid droplets
  • lipid droplet size in adipoctyes is about 2-3-fold smaller than in wild-type
• abnormal gonadal fat pad morphology (MGI Ref ID J:75192)
  • underdeveloped peri-gonadal fat pads
• abnormal mammary fat pad morphology (MGI Ref ID J:75192)
  • at 36 weeks of age on a high fat diet, mammary gland 4 fat is severely perturbed in females, with reduced numbers of adipoctyes that are heterogeneous in size and marked interstitial fibrosis and hypercellularity
• decreased adipose tissue amount (MGI Ref ID J:75192)
  • 2-fold reduction in the fat-to-water ratio
  • at 35 weeks of age on a high fat diet, mutants only show minor gains in fat mass compared to wild-type and have dramatically reduced adiposity in all fat pads compared to wild-type
• decreased subcutaneous adipose tissue amount (MGI Ref ID J:75192)
  • underdeveloped subcutaneous fat pads
  • at 36 weeks of age on a high fat diet, subcutaneous fat is severely perturbed in females, with reduced numbers of adipoctyes that are heterogeneous in size and marked interstitial fibrosis and hypercellularity
• decreased white adipose tissue amount (MGI Ref ID J:75192)
  • at 12 weeks of age on a high fat diet, mutants exhibit a 2-fold reduction in female mammary gland/subcutaneous WAT
• increased brown adipose tissue amount (MGI Ref ID J:75192)
  • mutants on a high fat diet exhibit hyperplastic brown adipose tissue, putatively secondary to elevated triglyceride levels
• cellular phenotype
• absent caveolae (MGI Ref ID J:75192)
  • adipocytes from peri-gonadal white adipose tissue show barren membrane architecture indicating a loss of caveolae
• growth/size phenotype
• decreased body weight (MGI Ref ID J:75192)
  • mice are leaner than wild-type mice on a chow diet
  • relative decrease in weight is exacerbated on a high fat diet
  • resistance to diet-induced obesity due to an inability to convert lipoprotein triglycerides into the fat droplet storage form
• postnatal slow weight gain (MGI Ref ID J:75192)
  • lack of weight gain
• resistance to diet-induced obesity (MGI Ref ID J:75192)
  • mutants are resistant to obesity when challenged with a high fat diet for 36 weeks
• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype (MGI Ref ID J:75192)
  • plasma glucose, insulin, and cholesterol levels were similar to wild type in both fasting and post-prandial states at 12 weeks of age, standard chow diet plasma glucose, insulin, and cholesterol levels were similar to wild-type in both fasting and post-prandial states at 12 weeks of age, standard chow diet
  • mutants do not exhibit significant changes in paremeters of energy expenditure such as VO2, VCO2, respiratory quotient, heat release, or movement, indicating that leanness is not due to increased energy expenditure
• abnormal blood chemistry (MGI Ref ID J:75192)
  • plasma ACRP30 (an adipoctye secreted factor) levels are reduced by 8-10 fold
• abnormal circulating free fatty acids level (MGI Ref ID J:75192)
  • free fatty acids levels fail to undergo the expected post-eating reduction seen in wild-type
• decreased circulating leptin level (MGI Ref ID J:75192)
  • plasma leptin levels are reduced more than 2-fold
• increased circulating triglyceride level (MGI Ref ID J:75192)
  • triglyceride levels are elevated in the fasted state and increased even more post-prandially, due to perturbed lipoprotein lipase activity
• increased circulating VLDL triglyceride level (MGI Ref ID J:75192)
  • the chylomicron/VLDL fraction of triglycerides is increased during fasting and increases dramatically above wild-type mice in the post-prandial state
• abnormal lipid homeostasis (MGI Ref ID J:75192)
  • mutants show kinetically delayed clearance of triglycerides in an oral fat tolerance test
• abnormal circulating free fatty acids level (MGI Ref ID J:75192)
  • free fatty acids levels fail to undergo the expected post-eating reduction seen in wild-type
• increased circulating triglyceride level (MGI Ref ID J:75192)
  • triglyceride levels are elevated in the fasted state and increased even more post-prandially, due to perturbed lipoprotein lipase activity
• increased circulating VLDL triglyceride level (MGI Ref ID J:75192)
  • the chylomicron/VLDL fraction of triglycerides is increased during fasting and increases dramatically above wild-type mice in the post-prandial state
• resistance to diet-induced obesity (MGI Ref ID J:75192)
  • mutants are resistant to obesity when challenged with a high fat diet for 36 weeks
• behavior/neurological phenotype
• increased eating behavior (MGI Ref ID J:75192)
  • daily food intake is higher in females
• endocrine/exocrine gland phenotype
• abnormal mammary gland morphology (MGI Ref ID J:75192)
  • the number of mammary ducts per field is increased
  • the mammary ductal epithelia exhibits hyperproliferation
  • size of mammary glands is reduced, however overall architecture is intact
• reproductive system phenotype
• abnormal mammary gland morphology (MGI Ref ID J:75192)
  • the number of mammary ducts per field is increased
  • the mammary ductal epithelia exhibits hyperproliferation
  • size of mammary glands is reduced, however overall architecture is intact
• skin/coat/nails phenotype
• abnormal hypodermis morphology (MGI Ref ID J:75192)
  • the hypodermal fat layer is absent in both males and females at 12 weeks of age
• liver/biliary system phenotype
• *normal* liver/biliary system phenotype (MGI Ref ID J:75192)
  • livers show no increase in weight or steatosis

Cav1^tm1Mls/Cav1^tm1Mls

        involves: 129/Sv * C57BL/6J * SJL

• growth/size phenotype
• decreased body weight (MGI Ref ID J:84260)
  • a defect in insulin-regulated lipogenesis contributes to the lean phenotype
• homeostasis/metabolism phenotype
• increased circulating insulin level (MGI Ref ID J:84260)
  • post-prandial serum levels of insulin were increased in mice that had been on a high fat diet for 9 months
• insulin resistance (MGI Ref ID J:84260)
  • mutants show a blunted decline in glucose levels upon insulin injection

View Research Applications

Research Applications

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

Cav1^tm1Mls related

Cardiovascular Research
Hypertriglyceridemia
Vascular Defects

Developmental Biology Research
Growth Defects

Diabetes and Obesity Research
Obesity Without Diabetes (diet-induced, resistant)

Internal/Organ Research
Adipose Defects

Metabolism Research
Lipid Metabolism

Genes & Alleles

Gene & Allele Information

Allele Symbol		Cav1tm1Mls
Allele Name		targeted mutation 1, Michael P Lisanti
Allele Type		Targeted (knock-out)
Common Name(s)		Cav-1 KO; Cav-1-;
Mutation Made By		Michael Lisanti,   The Albert Einstein College of Medicine
Strain of Origin		STOCK 129/Sv and C57BL/6J and SJL
ES Cell Line Name		WW6
ES Cell Line Strain		STOCK 129/Sv and C57BL/6J and SJL
Gene Symbol and Name		Cav1, caveolin 1, caveolae protein
Chromosome		6
Gene Common Name(s)		CAV; Cav-1; MGC187299; MSTP085; VIP21; caveolin-1;
Molecular Note		A 2.2 kb region of the gene including exons 1 and 2 and part of the promoter region was replaced with a neo resistance cassette via homologous recombination. Absence of gene expression in homozygous mutant animals was verified by Western blot analysis ofheart, adipose, and lung tissue, and also of mouse embryonic fibroblasts cultured from E13.5 homozygous mutant embryos. [MGI Ref ID J:75193]

Genotyping

Genotyping Information

Genotyping Protocols

Cav1^tm1Mls, SEP PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Razani B; Engelman JA; Wang XB; Schubert W; Zhang XL; Marks CB; Macaluso F; Russell RG; Li M; Pestell RG; Di Vizio D; Hou H Jr; Kneitz B; Lagaud G; Christ GJ; Edelmann W; Lisanti MP. 2001. Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J Biol Chem 276(41):38121-38. [PubMed: 11457855]  [MGI Ref ID J:75193]

Additional References

Capozza F; Williams TM; Schubert W; McClain S; Bouzahzah B; Sotgia F; Lisanti MP. 2003. Absence of caveolin-1 sensitizes mouse skin to carcinogen-induced epidermal hyperplasia and tumor formation. Am J Pathol 162(6):2029-39. [PubMed: 12759258]  [MGI Ref ID J:83485]

Cohen AW; Razani B; Schubert W; Williams TM; Wang XB; Iyengar P; Brasaemle DL; Scherer PE; Lisanti MP. 2004. Role of caveolin-1 in the modulation of lipolysis and lipid droplet formation. Diabetes 53(5):1261-70. [PubMed: 15111495]  [MGI Ref ID J:89326]

Cohen AW; Razani B; Wang XB; Combs TP; Williams TM; Scherer PE; Lisanti MP. 2003. Caveolin-1-deficient mice show insulin resistance and defective insulin receptor protein expression in adipose tissue. Am J Physiol Cell Physiol 285(1):C222-35. [PubMed: 12660144]  [MGI Ref ID J:84260]

Park DS; Woodman SE; Schubert W; Cohen AW; Frank PG; Chandra M; Shirani J; Razani B; Tang B; Jelicks LA; Factor SM; Weiss LM; Tanowitz HB; Lisanti MP. 2002. Caveolin-1/3 double-knockout mice are viable, but lack both muscle and non-muscle caveolae, and develop a severe cardiomyopathic phenotype. Am J Pathol 160(6):2207-17. [PubMed: 12057923]  [MGI Ref ID J:77372]

Razani B; Combs TP; Wang XB; Frank PG; Park DS; Russell RG; Li M; Tang B; Jelicks LA; Scherer PE; Lisanti MP. 2002. Caveolin-1-deficient Mice Are Lean, Resistant to Diet-induced Obesity, and Show Hypertriglyceridemia with Adipocyte Abnormalities. J Biol Chem 277(10):8635-47. [PubMed: 11739396]  [MGI Ref ID J:75192]

Schubert W; Frank PG; Woodman SE; Hyogo H; Cohen DE; Chow CW; Lisanti MP. 2002. Microvascular hyperpermeability in caveolin-1 (-/-) knock-out mice. Treatment with a specific nitric-oxide synthase inhibitor, L-name, restores normal microvascular permeability in Cav-1 null mice. J Biol Chem 277(42):40091-8. [PubMed: 12167625]  [MGI Ref ID J:79595]

Cav1^tm1Mls related

Adebiyi A; Zhao G; Cheranov SY; Ahmed A; Jaggar JH. 2007. Caveolin-1 abolishment attenuates the myogenic response in murine cerebral arteries. Am J Physiol Heart Circ Physiol 292(3):H1584-92. [PubMed: 17098833]  [MGI Ref ID J:120603]

Albinsson S; Nordstrom I; Sward K; Hellstrand P. 2008. Differential dependence of stretch and shear stress signaling on caveolin-1 in the vascular wall. Am J Physiol Cell Physiol 294(1):C271-9. [PubMed: 17989209]  [MGI Ref ID J:130507]

Bianco C; Strizzi L; Mancino M; Watanabe K; Gonzales M; Hamada S; Raafat A; Sahlah L; Chang C; Sotgia F; Normanno N; Lisanti M; Salomon DS. 2008. Regulation of Cripto-1 signaling and biological activity by caveolin-1 in mammary epithelial cells. Am J Pathol 172(2):345-57. [PubMed: 18202186]  [MGI Ref ID J:131372]

Boyan BD; Wong KL; Wang L; Yao H; Guldberg RE; Drab M; Jo H; Schwartz Z. 2006. Regulation of growth plate chondrocytes by 1,25-dihydroxyvitamin D3 requires caveolae and caveolin-1. J Bone Miner Res 21(10):1637-47. [PubMed: 16995819]  [MGI Ref ID J:128103]

Capozza F; Williams TM; Schubert W; McClain S; Bouzahzah B; Sotgia F; Lisanti MP. 2003. Absence of caveolin-1 sensitizes mouse skin to carcinogen-induced epidermal hyperplasia and tumor formation. Am J Pathol 162(6):2029-39. [PubMed: 12759258]  [MGI Ref ID J:83485]

Chow AK; Cena J; El-Yazbi AF; Crawford BD; Holt A; Cho WJ; Daniel EE; Schulz R. 2007. Caveolin-1 inhibits matrix metalloproteinase-2 activity in the heart. J Mol Cell Cardiol 42(4):896-901. [PubMed: 17349656]  [MGI Ref ID J:120811]

Cohen AW; Park DS; Woodman SE; Williams TM; Chandra M; Shirani J; Pereira de Souza A; Kitsis RN; Russell RG; Weiss LM; Tang B; Jelicks LA; Factor SM; Shtutin V; Tanowitz HB; Lisanti MP. 2003. Caveolin-1 null mice develop cardiac hypertrophy with hyperactivation of p42/44 MAP kinase in cardiac fibroblasts. Am J Physiol Cell Physiol 284(2):C457-74. [PubMed: 12388077]  [MGI Ref ID J:82042]

Cohen AW; Razani B; Schubert W; Williams TM; Wang XB; Iyengar P; Brasaemle DL; Scherer PE; Lisanti MP. 2004. Role of caveolin-1 in the modulation of lipolysis and lipid droplet formation. Diabetes 53(5):1261-70. [PubMed: 15111495]  [MGI Ref ID J:89326]

Cohen AW; Razani B; Wang XB; Combs TP; Williams TM; Scherer PE; Lisanti MP. 2003. Caveolin-1-deficient mice show insulin resistance and defective insulin receptor protein expression in adipose tissue. Am J Physiol Cell Physiol 285(1):C222-35. [PubMed: 12660144]  [MGI Ref ID J:84260]

Cohen AW; Schubert W; Brasaemle DL; Scherer PE; Lisanti MP. 2005. Caveolin-1 expression is essential for proper nonshivering thermogenesis in brown adipose tissue. Diabetes 54(3):679-86. [PubMed: 15734843]  [MGI Ref ID J:105133]

Costa MJ; Senou M; Van Rode F; Ruf J; Capello M; Dequanter D; Lothaire P; Dessy C; Dumont JE; Many MC; Van Sande J. 2007. Reciprocal negative regulation between thyrotropin/3',5'-cyclic adenosine monophosphate-mediated proliferation and caveolin-1 expression in human and murine thyrocytes. Mol Endocrinol 21(4):921-32. [PubMed: 17202321]  [MGI Ref ID J:119709]

El-Yazbi AF; Cho WJ; Boddy G; Daniel EE. 2005. Caveolin-1 gene knockout impairs nitrergic function in mouse small intestine. Br J Pharmacol 145(8):1017-26. [PubMed: 15937515]  [MGI Ref ID J:114334]

El-Yazbi AF; Cho WJ; Boddy G; Schulz R; Daniel EE. 2006. Impact of caveolin-1 knockout on NANC relaxation in circular muscles of the mouse small intestine compared with longitudinal muscles. Am J Physiol Gastrointest Liver Physiol 290(2):G394-403. [PubMed: 16166342]  [MGI Ref ID J:106049]

El-Yazbi AF; Cho WJ; Schulz R; Daniel EE. 2006. Caveolin-1 knockout alters beta-adrenoceptors function in mouse small intestine. Am J Physiol Gastrointest Liver Physiol 291(6):G1020-30. [PubMed: 16782699]  [MGI Ref ID J:116899]

Frank PG; Cheung MW; Pavlides S; Llaverias G; Park DS; Lisanti MP. 2006. Caveolin-1 and regulation of cellular cholesterol homeostasis. Am J Physiol Heart Circ Physiol 291(2):H677-86. [PubMed: 16603689]  [MGI Ref ID J:116292]

Frank PG; Lee H; Park DS; Tandon NN; Scherer PE; Lisanti MP. 2004. Genetic ablation of caveolin-1 confers protection against atherosclerosis. Arterioscler Thromb Vasc Biol 24(1):98-105. [PubMed: 14563650]  [MGI Ref ID J:101788]

Frank PG; Pavlides S; Cheung MW; Daumer K; Lisanti MP. 2008. Role of caveolin-1 in the regulation of lipoprotein metabolism. Am J Physiol Cell Physiol 295(1):C242-8. [PubMed: 18508910]  [MGI Ref ID J:138644]

Garrean S; Gao XP; Brovkovych V; Shimizu J; Zhao YY; Vogel SM; Malik AB. 2006. Caveolin-1 regulates NF-kappaB activation and lung inflammatory response to sepsis induced by lipopolysaccharide. J Immunol 177(7):4853-60. [PubMed: 16982927]  [MGI Ref ID J:139304]

Gioiosa L; Raggi C; Ricceri L; Jasmin JF; Frank PG; Capozza F; Lisanti MP; Alleva E; Sargiacomo M; Laviola G. 2008. Altered emotionality, spatial memory and cholinergic function in caveolin-1 knock-out mice. Behav Brain Res 188(2):255-262. [PubMed: 18083242]  [MGI Ref ID J:131303]

Gonzalez MI; Krizman-Genda E; Robinson MB. 2007. Caveolin-1 regulates the delivery and endocytosis of the glutamate transporter, excitatory amino acid carrier 1. J Biol Chem 282(41):29855-65. [PubMed: 17715130]  [MGI Ref ID J:126756]

Grande-Garcia A; Echarri A; de Rooij J; Alderson NB; Waterman-Storer CM; Valdivielso JM; del Pozo MA. 2007. Caveolin-1 regulates cell polarization and directional migration through Src kinase and Rho GTPases. J Cell Biol 177(4):683-94. [PubMed: 17517963]  [MGI Ref ID J:134719]

Hassan GS; Jasmin JF; Schubert W; Frank PG; Lisanti MP. 2004. Caveolin-1 deficiency stimulates neointima formation during vascular injury. Biochemistry 43(26):8312-21. [PubMed: 15222744]  [MGI Ref ID J:115492]

Hassan GS; Williams TM; Frank PG; Lisanti MP. 2006. Caveolin-1-deficient aortic smooth muscle cells show cell autonomous abnormalities in proliferation, migration, and endothelin-bases signal transduction Am J Physiol Heart Circ Physiol 290(6):H2393-401. [PubMed: 16415072]  [MGI Ref ID J:111840]

Heimerl S; Liebisch G; Le Lay S; Bottcher A; Wiesner P; Lindtner S; Kurzchalia TV; Simons K; Schmitz G. 2008. Caveolin-1 deficiency alters plasma lipid and lipoprotein profiles in mice. Biochem Biophys Res Commun 367(4):826-33. [PubMed: 18191037]  [MGI Ref ID J:131294]

Hu G; Ye RD; Dinauer MC; Malik AB; Minshall RD. 2008. Neutrophil caveolin-1 expression contributes to mechanism of lung inflammation and injury. Am J Physiol Lung Cell Mol Physiol 294(2):L178-86. [PubMed: 17993589]  [MGI Ref ID J:132206]

Jasmin JF; Malhotra S; Singh Dhallu M; Mercier I; Rosenbaum DM; Lisanti MP. 2007. Caveolin-1 deficiency increases cerebral ischemic injury. Circ Res 100(5):721-9. [PubMed: 17293479]  [MGI Ref ID J:133702]

Le Lay S; Kurzchalia TV. 2005. Getting rid of caveolins: phenotypes of caveolin-deficient animals. Biochim Biophys Acta 1746(3):322-33. [PubMed: 16019085]  [MGI Ref ID J:104846]

Le Saux CJ; Teeters K; Miyasato SK; Hoffmann PR; Bollt O; Douet V; Shohet RV; Broide DH; Tam EK. 2008. Down-regulation of caveolin-1, an inhibitor of transforming growth factor-beta signaling, in acute allergen-induced airway remodeling. J Biol Chem 283(9):5760-8. [PubMed: 18056268]  [MGI Ref ID J:132297]

Lee H; Park DS; Razani B; Russell RG; Pestell RG; Lisanti MP. 2002. Caveolin-1 mutations (P132L and null) and the pathogenesis of breast cancer: caveolin-1 (P132L) behaves in a dominant-negative manner and caveolin-1 (-/-) null mice show mammary epithelial cell hyperplasia. Am J Pathol 161(4):1357-69. [PubMed: 12368209]  [MGI Ref ID J:109251]

Li T; Sotgia F; Vuolo MA; Li M; Yang WC; Pestell RG; Sparano JA; Lisanti MP. 2006. Caveolin-1 mutations in human breast cancer: functional association with estrogen receptor alpha-positive status. Am J Pathol 168(6):1998-2013. [PubMed: 16723714]  [MGI Ref ID J:110117]

Maniatis NA; Shinin V; Schraufnagel DE; Okada S; Vogel SM; Malik AB; Minshall RD. 2008. Increased pulmonary vascular resistance and defective pulmonary artery filling in caveolin-1-/- mice. Am J Physiol Lung Cell Mol Physiol 294(5):L865-73. [PubMed: 18192592]  [MGI Ref ID J:136587]

Medina FA; de Almeida CJ; Dew E; Li J; Bonuccelli G; Williams TM; Cohen AW; Pestell RG; Frank PG; Tanowitz HB; Lisanti MP. 2006. Caveolin-1-deficient mice show defects in innate immunity and inflammatory immune response during Salmonella enterica serovar Typhimurium infection. Infect Immun 74(12):6665-74. [PubMed: 16982844]  [MGI Ref ID J:115914]

Milovanova T; Chatterjee S; Hawkins BJ; Hong N; Sorokina EM; Debolt K; Moore JS; Madesh M; Fisher AB. 2008. Caveolae are an essential component of the pathway for endothelial cell signaling associated with abrupt reduction of shear stress. Biochim Biophys Acta 1783(10):1866-75. [PubMed: 18573285]  [MGI Ref ID J:140780]

Park DS; Cohen AW; Frank PG; Razani B; Lee H; Williams TM; Chandra M; Shirani J; De Souza AP; Tang B; Jelicks LA; Factor SM; Weiss LM; Tanowitz HB; Lisanti MP. 2003. Caveolin-1 Null (-/-) Mice Show Dramatic Reductions in Life Span. Biochemistry 42(51):15124-15131. [PubMed: 14690422]  [MGI Ref ID J:87282]

Park DS; Lee H; Frank PG; Razani B; Nguyen AV; Parlow AF; Russell RG; Hulit J; Pestell RG; Lisanti MP. 2002. Caveolin-1-deficient mice show accelerated mammary gland development during pregnancy, premature lactation, and hyperactivation of the Jak-2/STAT5a signaling cascade. Mol Biol Cell 13(10):3416-30. [PubMed: 12388746]  [MGI Ref ID J:120010]

Park DS; Woodman SE; Schubert W; Cohen AW; Frank PG; Chandra M; Shirani J; Razani B; Tang B; Jelicks LA; Factor SM; Weiss LM; Tanowitz HB; Lisanti MP. 2002. Caveolin-1/3 double-knockout mice are viable, but lack both muscle and non-muscle caveolae, and develop a severe cardiomyopathic phenotype. Am J Pathol 160(6):2207-17. [PubMed: 12057923]  [MGI Ref ID J:77372]

Pojoga LH; Yao TM; Sinha S; Ross RL; Lin JC; Raffetto JD; Adler GK; Williams GH; Khalil RA. 2008. Effect of dietary sodium on vasoconstriction and eNOS-mediated vascular relaxation in caveolin-1-deficient mice. Am J Physiol Heart Circ Physiol 294(3):H1258-65. [PubMed: 18178722]  [MGI Ref ID J:132392]

Razani B; Combs TP; Wang XB; Frank PG; Park DS; Russell RG; Li M; Tang B; Jelicks LA; Scherer PE; Lisanti MP. 2002. Caveolin-1-deficient Mice Are Lean, Resistant to Diet-induced Obesity, and Show Hypertriglyceridemia with Adipocyte Abnormalities. J Biol Chem 277(10):8635-47. [PubMed: 11739396]  [MGI Ref ID J:75192]

Razani B; Lisanti MP. 2001. Caveolin-deficient mice: insights into caveolar function human disease. J Clin Invest 108(11):1553-61. [PubMed: 11733547]  [MGI Ref ID J:73209]

Rosengren BI; Rippe A; Rippe C; Venturoli D; Sward K; Rippe B. 2006. Transvascular protein transport in mice lacking endothelial caveolae. Am J Physiol Heart Circ Physiol 291(3):H1371-7. [PubMed: 16501011]  [MGI Ref ID J:116286]

Schubert W; Frank PG; Razani B; Park DS; Chow CW; Lisanti MP. 2001. Caveolae-deficient Endothelial Cells Show Defects in the Uptake and Transport of Albumin in Vivo. J Biol Chem 276(52):48619-22. [PubMed: 11689550]  [MGI Ref ID J:73489]

Schubert W; Frank PG; Woodman SE; Hyogo H; Cohen DE; Chow CW; Lisanti MP. 2002. Microvascular hyperpermeability in caveolin-1 (-/-) knock-out mice. Treatment with a specific nitric-oxide synthase inhibitor, L-name, restores normal microvascular permeability in Cav-1 null mice. J Biol Chem 277(42):40091-8. [PubMed: 12167625]  [MGI Ref ID J:79595]

Schubert W; Sotgia F; Cohen AW; Capozza F; Bonuccelli G; Bruno C; Minetti C; Bonilla E; Dimauro S; Lisanti MP. 2007. Caveolin-1(-/-)- and caveolin-2(-/-)-deficient mice both display numerous skeletal muscle abnormalities, with tubular aggregate formation. Am J Pathol 170(1):316-33. [PubMed: 17200204]  [MGI Ref ID J:117199]

Sotgia F; Rui H; Bonuccelli G; Mercier I; Pestell RG; Lisanti MP. 2006. Caveolin-1, mammary stem cells, and estrogen-dependent breast cancers. Cancer Res 66(22):10647-51. [PubMed: 17108100]  [MGI Ref ID J:116126]

Sotgia F; Williams TM; Schubert W; Medina F; Minetti C; Pestell RG; Lisanti MP. 2006. Caveolin-1 deficiency (-/-) conveys premalignant alterations in mammary epithelia, with abnormal lumen formation, growth factor independence, and cell invasiveness. Am J Pathol 168(1):292-309. [PubMed: 16400031]  [MGI Ref ID J:104439]

Trushina E; Du Charme J; Parisi J; McMurray CT. 2006. Neurological abnormalities in caveolin-1 knock out mice. Behav Brain Res 172(1):24-32. [PubMed: 16750274]  [MGI Ref ID J:110712]

Volonte D; McTiernan CF; Drab M; Kasper M; Galbiati F. 2008. Caveolin-1 and caveolin-3 form heterooligomeric complexes in atrial cardiac myocytes that are required for doxorubicin-induced apoptosis. Am J Physiol Heart Circ Physiol 294(1):H392-401. [PubMed: 17982011]  [MGI Ref ID J:132310]

Wang MD; Kiss RS; Franklin V; McBride HM; Whitman SC; Marcel YL. 2007. Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathways. J Lipid Res 48(3):633-45. [PubMed: 17148552]  [MGI Ref ID J:120283]

Williams TM; Cheung MW; Park DS; Razani B; Cohen AW; Muller WJ; Di Vizio D; Chopra NG; Pestell RG; Lisanti MP. 2003. Loss of caveolin-1 gene expression accelerates the development of dysplastic mammary lesions in tumor-prone transgenic mice. Mol Biol Cell 14(3):1027-42. [PubMed: 12631721]  [MGI Ref ID J:132472]

Williams TM; Hassan GS; Li J; Cohen AW; Medina F; Frank PG; Pestell RG; Di Vizio D; Loda M; Lisanti MP. 2005. Caveolin-1 promotes tumor progression in an autochthonous mouse model of prostate cancer: genetic ablation of Cav-1 delays advanced prostate tumor development in tramp mice. J Biol Chem 280(26):25134-45. [PubMed: 15802273]  [MGI Ref ID J:133066]

Williams TM; Lee H; Cheung MW; Cohen AW; Razani B; Iyengar P; Scherer PE; Pestell RG; Lisanti MP. 2004. Combined loss of INK4a and caveolin-1 synergistically enhances cell proliferation and oncogene-induced tumorigenesis: role of INK4a/CAV-1 in mammary epithelial cell hyperplasia. J Biol Chem 279(23):24745-56. [PubMed: 15044451]  [MGI Ref ID J:90334]

Williams TM; Medina F; Badano I; Hazan RB; Hutchinson J; Muller WJ; Chopra NG; Scherer PE; Pestell RG; Lisanti MP. 2004. Caveolin-1 gene disruption promotes mammary tumorigenesis and dramatically enhances lung metastasis in vivo. Role of Cav-1 in cell invasiveness and matrix metalloproteinase (MMP-2/9) secretion. J Biol Chem 279(49):51630-46. [PubMed: 15355971]  [MGI Ref ID J:95195]

Williams TM; Sotgia F; Lee H; Hassan G; Di Vizio D; Bonuccelli G; Capozza F; Mercier I; Rui H; Pestell RG; Lisanti MP. 2006. Stromal and epithelial caveolin-1 both confer a protective effect against mammary hyperplasia and tumorigenesis: caveolin-1 antagonizes cyclin d1 function in mammary epithelial cells. Am J Pathol 169(5):1784-801. [PubMed: 17071600]  [MGI Ref ID J:114569]

Woodman SE; Ashton AW; Schubert W; Lee H; Williams TM; Medina FA; Wyckoff JB; Combs TP; Lisanti MP. 2003. Caveolin-1 knockout mice show an impaired angiogenic response to exogenous stimuli. Am J Pathol 162(6):2059-68. [PubMed: 12759260]  [MGI Ref ID J:109484]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB27

Colony Maintenance

Breeding & Husbandry	The resulting chimeric animals were crossed to C57BL/6J mice for approximately 5 generations. The donating investigator noted diminished reproductive performance as the backcross to C57BL/6J background progressed and backcrossed to a 129S6/SvEv background for 1 generation. The mice are now maintained as homozygotes and are primarily a mix of 129 and C57BL/6, but a minor contribution from the SJL background (contributed from the originating ES cell line) should not be discounted. Coat color expected from breeding: Black and Agouti.
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

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 ~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 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. 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
	101045 B6129SF2/J	(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.

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

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

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.