Cyp11b2

Summary

Gene Symbol: Cyp11b2
Description: cytochrome P450, family 11, subfamily b, polypeptide 2
Alias: Cpn2, Cyp11b, Cyp11b-2, cytochrome P450 11B2, mitochondrial, CYPXIB2, aldosterone synthase, cytochrome P450C11, steroid 11-beta-hydroxylase
Species: mouse
Products:     Cyp11b2

Top Publications

  1. Makhanova N, Lee G, Takahashi N, Sequeira Lopez M, Gomez R, Kim H, et al. Kidney function in mice lacking aldosterone. Am J Physiol Renal Physiol. 2006;290:F61-9 pubmed
    To explore the effects of decreased amounts or absence of aldosterone, we have disrupted the gene coding for aldosterone synthase (AS) in mice and investigated blood pressure and kidney function in AS+/+, AS+/-, and AS-/- mice...
  2. Lee G, Makhanova N, Caron K, Lopez M, Gomez R, Smithies O, et al. Homeostatic responses in the adrenal cortex to the absence of aldosterone in mice. Endocrinology. 2005;146:2650-6 pubmed
    ..of aldosterone on development and endocrine function, we have disrupted the mouse gene, Cyp11b2, coding for aldosterone synthase (AS) by replacing its first two exons with sequences coding for enhanced green fluorescent protein...
  3. Chadwick J, Swager S, Lowe J, Welc S, Tidball J, Gomez Sanchez C, et al. Myeloid cells are capable of synthesizing aldosterone to exacerbate damage in muscular dystrophy. Hum Mol Genet. 2016;25:5167-5177 pubmed publisher
    ..b>Aldosterone synthase protein levels are increased in leukocytes isolated from dystrophic muscles compared with controls and ..
  4. Cui S, Ross A, Stallings N, Parker K, Capel B, Quaggin S. Disrupted gonadogenesis and male-to-female sex reversal in Pod1 knockout mice. Development. 2004;131:4095-105 pubmed
    ..Our results establish that Pod1 is essential for gonadal development, and place it in a transcriptional network that orchestrates cell fate decisions in gonadal progenitors. ..
  5. Huang C, Miyagawa S, Matsumaru D, Parker K, Yao H. Progenitor cell expansion and organ size of mouse adrenal is regulated by sonic hedgehog. Endocrinology. 2010;151:1119-28 pubmed publisher
    ..Our results not only provide the genetic evidence to support that the adrenal capsule contributes to the growth of adrenocortex in both fetal and adult life but also identify a novel role of Shh in this process...
  6. Nesterov V, Dahlmann A, Krueger B, Bertog M, Loffing J, Korbmacher C. Aldosterone-dependent and -independent regulation of the epithelial sodium channel (ENaC) in mouse distal nephron. Am J Physiol Renal Physiol. 2012;303:F1289-99 pubmed publisher
    ..To investigate whether aldosterone is necessary for ENaC activity in the DCT2/CNT, we used aldosterone synthase knockout (AS(-/-)) mice that lack aldosterone...
  7. Lin E, Pentz E, Sequeira Lopez M, Gomez R. Aldo-keto reductase 1b7, a novel marker for renin cells, is regulated by cyclic AMP signaling. Am J Physiol Regul Integr Comp Physiol. 2015;309:R576-84 pubmed publisher
    ..This pattern of coexpression persists in extreme pathological situations, such as deletion of the genes for aldosterone synthase or Dicer...
  8. Bhaumik M, Seldin M, Stanley P. Cloning and chromosomal mapping of the mouse Mgat3 gene encoding N-acetylglucosaminyltransferase III. Gene. 1995;164:295-300 pubmed
    ..3-q13.1 in the human genome. Northern analyses of adult tissues showed that Mgat3 is expressed at high levels in kidney and brain, and at lower levels in many other tissues. ..
  9. Kurt B, Karger C, Wagner C, Kurtz A. Control of renin secretion from kidneys with renin cell hyperplasia. Am J Physiol Renal Physiol. 2014;306:F327-32 pubmed publisher
    ..As a model, we used kidneys from mice lacking aldosterone synthase (AS?/? mice), which displayed 10-fold elevations of renin mRNA and plasma renin concentrations...

More Information

Publications44

  1. Freedman B, Kempna P, Carlone D, Shah M, Guagliardo N, Barrett P, et al. Adrenocortical zonation results from lineage conversion of differentiated zona glomerulosa cells. Dev Cell. 2013;26:666-673 pubmed publisher
    ..These findings demonstrate that adrenocortical zonation and regeneration result from lineage conversion and may provide a paradigm for homeostatic cellular renewal in other tissues. ..
  2. Karger C, Kurtz F, Steppan D, Schwarzensteiner I, Machura K, Angel P, et al. Procollagen I-expressing renin cell precursors. Am J Physiol Renal Physiol. 2013;305:F355-61 pubmed publisher
    ..As an experimental model, we used kidneys of aldosterone synthase-deficient mice, which display a prominent compensatory overproduction of renin cells that are arranged in ..
  3. Adam O, Zimmer C, Hanke N, Hartmann R, Klemmer B, Böhm M, et al. Inhibition of aldosterone synthase (CYP11B2) by torasemide prevents atrial fibrosis and atrial fibrillation in mice. J Mol Cell Cardiol. 2015;85:140-50 pubmed publisher
    ..Torasemide but not furosemide inhibited human aldosterone synthase (CYP11B2) activity in transfected lung fibroblasts (V79MZ cells) by 75±1.8%...
  4. Jeggle P, Hofschröer V, Maase M, Bertog M, Kusche Vihrog K. Aldosterone synthase knockout mouse as a model for sodium-induced endothelial sodium channel up-regulation in vascular endothelium. FASEB J. 2016;30:45-53 pubmed publisher
    ..we test whether high extracellular sodium per se increases EnNaC expression and cortical stiffness in an aldosterone synthase (Cyp11b2)-deficient (AS(-/-)) mouse model...
  5. Huang C, Kraft C, Moy N, Ng L, Forrest D. A Novel Population of Inner Cortical Cells in the Adrenal Gland That Displays Sexually Dimorphic Expression of Thyroid Hormone Receptor-β1. Endocrinology. 2015;156:2338-48 pubmed publisher
    ..TRβ1-deficient mice were resistant to these actions of T3, supporting a functional role for TRβ1 in the inner cortex. ..
  6. Inglis G, Kenyon C, Szpirer C, Klinga Levan K, Sutcliffe R, Connell J. Microsatellite polymorphism analysis allows the individual assignment of the rat 11 beta-hydroxylase gene (Cyp11b1) and the rat aldosterone synthase gene (Cyp11b2) to chromosome 7 using rat x mouse somatic cell hybrids and identifies differences betw. J Mol Endocrinol. 1995;14:303-11 pubmed
    ..were used to determine the chromosomal location of the rat genes encoding 11 beta-hydroxylase and aldosterone synthase (Cyp11b1 and Cyp11b2 respectively)...
  7. El Moghrabi S, Houillier P, Picard N, Sohet F, Wootla B, Bloch Faure M, et al. Tissue kallikrein permits early renal adaptation to potassium load. Proc Natl Acad Sci U S A. 2010;107:13526-31 pubmed publisher
    ..Using aldosterone synthase-deficient mice, we confirmed that the control of TK secretion is aldosterone-independent...
  8. Keeney D, Jenkins C, Waterman M. Developmentally regulated expression of adrenal 17 alpha-hydroxylase cytochrome P450 in the mouse embryo. Endocrinology. 1995;136:4872-9 pubmed
    ..mRNAs) encoding all of the steroid hydroxylases required to produce cortisol and corticosterone but little aldosterone synthase mRNA...
  9. King P, Paul A, Laufer E. Shh signaling regulates adrenocortical development and identifies progenitors of steroidogenic lineages. Proc Natl Acad Sci U S A. 2009;106:21185-90 pubmed publisher
    ..Our findings both support a novel dual lineage, Shh-independent and Shh-dependent, model of adrenocortical development, and identify distinct populations of adrenocortical progenitor and candidate stem cells...
  10. Kim A, Reuter A, Zubair M, Else T, Serecky K, Bingham N, et al. Targeted disruption of beta-catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex. Development. 2008;135:2593-602 pubmed publisher
    ..These results define crucial roles for beta-catenin--presumably as part of the Wnt canonical signaling pathway--in both embryonic development of the adrenal cortex and in maintenance of the adult organ. ..
  11. Tevosian S, Jiménez E, Hatch H, Jiang T, Morse D, Fox S, et al. Adrenal Development in Mice Requires GATA4 and GATA6 Transcription Factors. Endocrinology. 2015;156:2503-17 pubmed publisher
    ..Our results reveal a requirement for GATA factors in adrenal development and provide a novel tool to characterize the transcriptional network controlling adrenocortical cell fates. ..
  12. Pihlajoki M, Gretzinger E, Cochran R, Kyrönlahti A, Schrade A, Hiller T, et al. Conditional mutagenesis of Gata6 in SF1-positive cells causes gonadal-like differentiation in the adrenal cortex of mice. Endocrinology. 2013;154:1754-67 pubmed publisher
    ..Our findings offer genetic proof that GATA6 regulates the differentiation of steroidogenic progenitors into adrenocortical cells. ..
  13. Huby A, Antonova G, Groenendyk J, Gomez Sanchez C, Bollag W, Filosa J, et al. Adipocyte-Derived Hormone Leptin Is a Direct Regulator of Aldosterone Secretion, Which Promotes Endothelial Dysfunction and Cardiac Fibrosis. Circulation. 2015;132:2134-45 pubmed publisher
    ..We hypothesized that the adipokine leptin is a direct regulator of aldosterone synthase (CYP11B2) expression and aldosterone release and promotes cardiovascular dysfunction via aldosterone-..
  14. Wong M, Rice D, Parker K, Schimmer B. The roles of cAMP and cAMP-dependent protein kinase in the expression of cholesterol side chain cleavage and steroid 11 beta-hydroxylase genes in mouse adrenocortical tumor cells. J Biol Chem. 1989;264:12867-71 pubmed
    ..These results strongly support the hypothesis that impaired expression of steroidogenic enzymes in the Kin mutants results directly from defects in cAMP-dependent protein kinase activity. ..
  15. Allen R, Carey C, Parker J, Mortrud M, Mellon S, Low M. Targeted ablation of pituitary pre-proopiomelanocortin cells by herpes simplex virus-1 thymidine kinase differentially regulates mRNAs encoding the adrenocorticotropin receptor and aldosterone synthase in the mouse adrenal gland. Mol Endocrinol. 1995;9:1005-16 pubmed
    ..pituitary POMC cell ablation resulted in the decrease of adrenal p450c11 beta transcripts while p450c11AS (aldosterone synthase) mRNA levels remained constant...
  16. Veronneau S, Bernard H, Cloutier M, Courtemanche J, Ducharme L, Lefebvre A, et al. The hamster adrenal cytochrome P450C11 has equipotent 11beta-hydroxylase and 19-hydroxylase activities, but no aldosterone synthase activity. J Steroid Biochem Mol Biol. 1996;57:125-39 pubmed
  17. Luther J, Luo P, Kreger M, Brissova M, Dai C, Whitfield T, et al. Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets. Diabetologia. 2011;54:2152-63 pubmed publisher
    ..We assessed insulin sensitivity and insulin secretion in aldosterone synthase-deficient (As [also known as Cyp11b2](-/-)) and wild-type mice using euglycaemic-hyperinsulinaemic and ..
  18. Takahashi N, Smithies O. Gene targeting approaches to analyzing hypertension. J Am Soc Nephrol. 1999;10:1598-605 pubmed
    ..These various gene targeting experiments help identify genes regulating BP, promote a better understanding of the pathophysiology of the condition, and help identify potential targets for therapies. ..
  19. Ambroisine M, Favre J, Oliviero P, Rodriguez C, Gao J, Thuillez C, et al. Aldosterone-induced coronary dysfunction in transgenic mice involves the calcium-activated potassium (BKCa) channels of vascular smooth muscle cells. Circulation. 2007;116:2435-43 pubmed
    Cardiomyocyte-specific overexpression of aldosterone synthase in male (MAS) mice induces a nitric oxide-independent coronary dysfunction...
  20. Makhanova N, Hagaman J, Kim H, Smithies O. Salt-sensitive blood pressure in mice with increased expression of aldosterone synthase. Hypertension. 2008;51:134-40 pubmed
    To study the effects of modestly increased expression of aldosterone synthase (AS), we generated mice (AS(hi/hi)) by replacing the 3' untranslated region of AS mRNA with that from a stable mRNA. AS(hi/hi) mice on a normal-salt diet had 1...
  21. Luther J, Luo P, Wang Z, Cohen S, Kim H, Fogo A, et al. Aldosterone deficiency and mineralocorticoid receptor antagonism prevent angiotensin II-induced cardiac, renal, and vascular injury. Kidney Int. 2012;82:643-51 pubmed publisher
    ..b>Aldosterone synthase knockout mice and wild-type littermates were treated with angiotensin II or vehicle plus the ..
  22. Bogerd A, Franklin A, Rice D, Schimmer B, Parker K. Identification and characterization of two upstream elements that regulate adrenocortical expression of steroid 11 beta-hydroxylase. Mol Endocrinol. 1990;4:845-50 pubmed
    ..These studies thus define two regulatory elements that play important roles in 11 beta-OHase expression. ..
  23. Morohashi K, Tsuboi Asai H, Matsushita S, Suda M, Nakashima M, Sasano H, et al. Structural and functional abnormalities in the spleen of an mFtz-F1 gene-disrupted mouse. Blood. 1999;93:1586-94 pubmed
    ..Our results indicate that a lack of the mFtz-F1 gene in mice is associated with structural and functional abnormalities of the splenic vascular system. ..
  24. Domalik L, Chaplin D, Kirkman M, Wu R, Liu W, Howard T, et al. Different isozymes of mouse 11 beta-hydroxylase produce mineralocorticoids and glucocorticoids. Mol Endocrinol. 1991;5:1853-61 pubmed
    ..two isozymes of mouse steroid 11 beta-hydroxylase (11 beta-OHase), designated 11 beta-OHase and aldosterone synthase (AS)...
  25. Venihaki M, Carrigan A, Dikkes P, Majzoub J. Circadian rise in maternal glucocorticoid prevents pulmonary dysplasia in fetal mice with adrenal insufficiency. Proc Natl Acad Sci U S A. 2000;97:7336-41 pubmed
  26. Martinerie L, Viengchareun S, Meduri G, Kim H, Luther J, Lombes M. Aldosterone postnatally, but not at birth, is required for optimal induction of renal mineralocorticoid receptor expression and sodium reabsorption. Endocrinology. 2011;152:2483-91 pubmed publisher
    ..aldosterone and corticosterone levels and renal MR expression by quantitative real-time PCR, between aldosterone synthase (AS) knockout, heterozygous, and wild type (WT) mice, at birth and postnatal d 8...
  27. Cole T, Blendy J, Monaghan A, Krieglstein K, Schmid W, Aguzzi A, et al. Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation. Genes Dev. 1995;9:1608-21 pubmed
    ..cortical steroid biosynthetic enzymes, such as side-chain cleavage enzyme, steroid 11 beta-hydroxylase, and aldosterone synthase. Adrenal glands lack a central medulla and synthesize no adrenaline...
  28. Bassett M, Zhang Y, Clyne C, White P, Rainey W. Differential regulation of aldosterone synthase and 11beta-hydroxylase transcription by steroidogenic factor-1. J Mol Endocrinol. 2002;28:125-35 pubmed
    11beta-Hydroxylase (hCYP11B1) and aldosterone synthase (hCYP11B2) are closely related isozymes with distinct roles in cortisol and aldosterone production respectively...
  29. Mouw A, Rice D, Meade J, Chua S, White P, Schimmer B, et al. Structural and functional analysis of the promoter region of the gene encoding mouse steroid 11 beta-hydroxylase. J Biol Chem. 1989;264:1305-9 pubmed
    ..These experiments thus present a useful system for the investigation of cis-acting elements involved in the transcriptional regulation of 11 beta-OHase. ..
  30. Machura K, Iankilevitch E, Neubauer B, Theuring F, Kurtz A. The aldo-keto reductase AKR1B7 coexpresses with renin without influencing renin production and secretion. Am J Physiol Renal Physiol. 2013;304:F578-84 pubmed publisher
    ..In summary, our data suggest that AKR1B7 is not of major relevance for the regulation of renin production and secretion in spite of its striking coregulation with renin expression. ..
  31. Paul A, Laufer E. Endogenous biotin as a marker of adrenocortical cells with steroidogenic potential. Mol Cell Endocrinol. 2011;336:133-40 pubmed publisher
    ..Fluorescent streptavidin applied using a simple one-step staining protocol thus provides a potent counterstain for use in adrenal analyses. ..
  32. Takase M, Ukena K, Tsutsui K. Expression and localization of cytochrome P450(11beta,aldo) mRNA in the frog brain. Brain Res. 2002;950:288-96 pubmed
    ..These results taken together suggest that the frog brain synthesizes adrenal steroids, such as corticosterone and aldosterone. ..
  33. Heikkilä M, Peltoketo H, Leppäluoto J, Ilves M, Vuolteenaho O, Vainio S. Wnt-4 deficiency alters mouse adrenal cortex function, reducing aldosterone production. Endocrinology. 2002;143:4358-65 pubmed
    ..5 onward, especially in the outermost part. Expression of Cyp11B2 and preadipocyte factor 1 is lowered in the glands of Wnt-4 mutant animals, resulting in significantly reduced ..
  34. Luo P, DeMatteo A, Wang Z, Zhu L, Wang A, Kim H, et al. Aldosterone deficiency prevents high-fat-feeding-induced hyperglycaemia and adipocyte dysfunction in mice. Diabetologia. 2013;56:901-10 pubmed publisher
    ..Wild-type and aldosterone synthase-deficient (As (-/-)) mice were fed a high-fat (HF) or normal chow diet for 12 weeks...
  35. Makhanova N, Sequeira Lopez M, Gomez R, Kim H, Smithies O. Disturbed homeostasis in sodium-restricted mice heterozygous and homozygous for aldosterone synthase gene disruption. Hypertension. 2006;48:1151-9 pubmed
    We have determined that differences in expression of aldosterone synthase (AS) affect responses to a low-salt diet. In AS-null mice (AS(-/-)), but not in wild-type, low salt significantly decreased plasma sodium and increased potassium...