desoxycorticosterone

Summary

Summary: A steroid metabolite that is the 11-deoxy derivative of CORTICOSTERONE and the 21-hydroxy derivative of PROGESTERONE

Top Publications

  1. Khisti R, Boyd K, Kumar S, Morrow A. Systemic ethanol administration elevates deoxycorticosterone levels and chronic ethanol exposure attenuates this response. Brain Res. 2005;1049:104-11 pubmed
    ..These findings suggest that acute ethanol increases DOC levels in ethanol naïve rats and chronic ethanol consumption induces tolerance to ethanol-induced increases in DOC levels. ..
  2. Porcu P, O Buckley T, Alward S, Song S, Grant K, de Wit H, et al. Differential effects of ethanol on serum GABAergic 3alpha,5alpha/3alpha,5beta neuroactive steroids in mice, rats, cynomolgus monkeys, and humans. Alcohol Clin Exp Res. 2010;34:432-42 pubmed publisher
    ..Rats are unique in their pronounced elevation of GABAergic neuroactive steroids, while this effect was not observed in mice or cynomolgus monkeys at comparable ethanol doses. ..
  3. Callera G, Tostes R, Yogi A, Montezano A, Touyz R. Endothelin-1-induced oxidative stress in DOCA-salt hypertension involves NADPH-oxidase-independent mechanisms. Clin Sci (Lond). 2006;110:243-53 pubmed
    ..Mitochondria may play a role in ET-1-driven oxidative stress, as evidenced by increased mitochondrial-derived ROS in this model of hypertension. ..
  4. Porcu P, Grant K, Green H, Rogers L, Morrow A. Hypothalamic-pituitary-adrenal axis and ethanol modulation of deoxycorticosterone levels in cynomolgus monkeys. Psychopharmacology (Berl). 2006;186:293-301 pubmed
    ..These results suggest that DOC levels in monkeys are regulated by the HPA axis and may contribute to physiological responses following activation. ..
  5. Giachini F, Sullivan J, Lima V, Carneiro F, Fortes Z, Pollock D, et al. Extracellular signal-regulated kinase 1/2 activation, via downregulation of mitogen-activated protein kinase phosphatase 1, mediates sex differences in desoxycorticosterone acetate-salt hypertension vascular reactivity. Hypertension. 2010;55:172-9 pubmed publisher
    ..Uninephrectomized male and female Sprague-Dawley rats received desoxycorticosterone acetate (DOCA) pellets (200 mg per animal) and saline to drink for 3 weeks...
  6. Diaz J, Ni W, Thompson J, King A, Fink G, Watts S. 5-Hydroxytryptamine lowers blood pressure in normotensive and hypertensive rats. J Pharmacol Exp Ther. 2008;325:1031-8 pubmed publisher
    ..5 g/l in water) prevented the fall in blood pressure to 5-HT. We conclude that chronic exogenous 5-HT reduces blood pressure in normotensive and hypertensive rats through mechanisms critically dependent on NOS. ..
  7. Porcu P, O Buckley T, Leslie Morrow A, Adinoff B. Differential hypothalamic-pituitary-adrenal activation of the neuroactive steroids pregnenolone sulfate and deoxycorticosterone in healthy controls and alcohol-dependent subjects. Psychoneuroendocrinology. 2008;33:214-26 pubmed
    ..Further, alcohol-dependent patients show a blunted PREG-S response to adrenal stimulation and a delayed deoxycorticosterone response to oCRH challenge. ..
  8. Jin L, Beswick R, Yamamoto T, Palmer T, Taylor T, Pollock J, et al. Increased reactive oxygen species contributes to kidney injury in mineralocorticoid hypertensive rats. J Physiol Pharmacol. 2006;57:343-57 pubmed
    ..These data suggest that renal injury characteristic of mineralocorticoid hypertension is associated with oxidative stress and is partly independent of blood pressure. ..
  9. Hardoy M, Serra M, Carta M, Contu P, Pisu M, Biggio G. Increased neuroactive steroid concentrations in women with bipolar disorder or major depressive disorder. J Clin Psychopharmacol. 2006;26:379-84 pubmed
    ..These differences did not seem to be attributable simply to drug treatment or to comorbidity with other psychiatric conditions in the patients. ..

More Information

Publications62

  1. Viel E, Benkirane K, Javeshghani D, Touyz R, Schiffrin E. Xanthine oxidase and mitochondria contribute to vascular superoxide anion generation in DOCA-salt hypertensive rats. Am J Physiol Heart Circ Physiol. 2008;295:H281-8 pubmed publisher
    ..Our findings demonstrate the involvement of ET(A) receptor-modulated O(2)(*-) derived from XO and from mitochondrial oxidative enzymes in arteries from DOCA-salt rats. ..
  2. Sahan Firat S, Jennings B, Yaghini F, Song C, Estes A, Fang X, et al. 2,3',4,5'-Tetramethoxystilbene prevents deoxycorticosterone-salt-induced hypertension: contribution of cytochrome P-450 1B1. Am J Physiol Heart Circ Physiol. 2010;299:H1891-901 pubmed publisher
  3. Zhang A, Jia Z, Guo X, Yang T. Aldosterone induces epithelial-mesenchymal transition via ROS of mitochondrial origin. Am J Physiol Renal Physiol. 2007;293:F723-31 pubmed
    ..These observations suggest that Aldo induces EMT via MR-mediated, mitochondrial-originated, ROS-dependent ERK1/2 activation in renal tubular epithelial cells. ..
  4. Szasz T, Linder A, Davis R, Burnett R, Fink G, Watts S. Allopurinol does not decrease blood pressure or prevent the development of hypertension in the deoxycorticosterone acetate-salt rat model. J Cardiovasc Pharmacol. 2010;56:627-34 pubmed publisher
    ..We conclude that XO does not play an important role in the development or maintenance of hypertension in the rat DOCA-salt hypertension model. ..
  5. Milla S, Jalabert B, Rime H, Prunet P, Bobe J. Hydration of rainbow trout oocyte during meiotic maturation and in vitro regulation by 17,20{beta}-dihydroxy-4-pregnen-3-one and cortisol. J Exp Biol. 2006;209:1147-56 pubmed
    ..Together, these results suggest that cortisol could participate in the control of oocyte hydration and possibly in other periovulatory ovarian functions. ..
  6. Sturm A, Bury N, Dengreville L, Fagart J, Flouriot G, Rafestin Oblin M, et al. 11-deoxycorticosterone is a potent agonist of the rainbow trout (Oncorhynchus mykiss) mineralocorticoid receptor. Endocrinology. 2005;146:47-55 pubmed publisher
    ..1 +/- 0.3 x 10(-9) and 3.7 +/- 1.9 x 10(-9) M, respectively). A similar response was observed in transactivation assays with rtMRb. These results are discussed in the view of reported circulating levels of corticosteroids in trout...
  7. Strohle A, Pasini A, Romeo E, Hermann B, Spalletta G, di Michele F, et al. Fluoxetine decreases concentrations of 3 alpha, 5 alpha-tetrahydrodeoxycorticosterone (THDOC) in major depression. J Psychiatr Res. 2000;34:183-6 pubmed
    ..Our results give further evidence for a disequilibrium of 3 alpha-reduced neuroactive steroids in major depression, which is normalized by treatment with fluoxetine. ..
  8. Xu H, Fink G, Galligan J. Tempol lowers blood pressure and sympathetic nerve activity but not vascular O2- in DOCA-salt rats. Hypertension. 2004;43:329-34 pubmed
    ..It is concluded that depressor responses and decreases in HR and RSNA caused by acute tempol treatment are caused by direct sympathetic nerve activity inhibition that is not accompanied by SOD-mimetic action in the aorta or vena cava. ..
  9. Serra M, Pisul M, Dazzi L, Purdy R, Biggio G. Prevention of the stress-induced increase in the concentration of neuroactive steroids in rat brain by long-term administration of mirtazapine but not of fluoxetine. J Psychopharmacol. 2002;16:133-8 pubmed
  10. Jiang J, Young G, Kobayashi T, Nagahama Y. Eel (Anguilla japonica) testis 11beta-hydroxylase gene is expressed in interrenal tissue and its product lacks aldosterone synthesizing activity. Mol Cell Endocrinol. 1998;146:207-11 pubmed
    ..Immunohistochemistry using an antiserum against P450(11beta) also revealed strong immunostaining in interrenal cells...
  11. Hiroi T, Kishimoto W, Chow T, Imaoka S, Igarashi T, Funae Y. Progesterone oxidation by cytochrome P450 2D isoforms in the brain. Endocrinology. 2001;142:3901-8 pubmed
    ..Collectively, our findings support the idea that cytochrome P450 2D may be involved in the regulation (metabolism and/or synthesis) of endogenous neuroactive steroids, such as progesterone and its derivatives, in brain tissues. ..
  12. Banes A, Watts S. Upregulation of arterial serotonin 1B and 2B receptors in deoxycorticosterone acetate-salt hypertension. Hypertension. 2002;39:394-8 pubmed
  13. Reddy D, Rogawski M. Stress-induced deoxycorticosterone-derived neurosteroids modulate GABA(A) receptor function and seizure susceptibility. J Neurosci. 2002;22:3795-805 pubmed
  14. O Dell L, Alomary A, Vallée M, Koob G, Fitzgerald R, Purdy R. Ethanol-induced increases in neuroactive steroids in the rat brain and plasma are absent in adrenalectomized and gonadectomized rats. Eur J Pharmacol. 2004;484:241-7 pubmed
    ..This response was followed by the further secretion of the anxiolytic neuroactive steroids allopregnanolone and allotetrahydrodeoxycorticosterone, both of which appeared to be of adrenal and gonadal origin. ..
  15. Banes A, Watts S. Enhanced contraction to 5-hydroxytryptamine is not due to "unmasking" of 5-hydroxytryptamine(1b) receptors in the mesenteric artery of the deoxycorticosterone acetate-salt rat. Hypertension. 2001;38:891-5 pubmed
    ..These data support the conclusions that 5-HT(1B) receptors mediate contraction in mesenteric arteries from hypertensive rats and that this enhanced response to 5-HT is not due to membrane depolarization alone. ..
  16. Verlander J, Hassell K, Royaux I, Glapion D, Wang M, Everett L, et al. Deoxycorticosterone upregulates PDS (Slc26a4) in mouse kidney: role of pendrin in mineralocorticoid-induced hypertension. Hypertension. 2003;42:356-62 pubmed
    ..We conclude that pendrin is upregulated with aldosterone analogues and is critical in the pathogenesis of mineralocorticoid-induced hypertension and metabolic alkalosis. ..
  17. Wang Q, Domenighetti A, Pedrazzini T, Burnier M. Potassium supplementation reduces cardiac and renal hypertrophy independent of blood pressure in DOCA/salt mice. Hypertension. 2005;46:547-54 pubmed
    ..In 2-renin gene, hypertensive mice, potassium supplementation also prevents the development of cardiac hypertrophy, but the effect cannot be separated from the decrease in BP. ..
  18. Hagenah G, Wündisch T, Eckstein E, Zimmermann S, Holst F, Grimm W, et al. [Sepsis-like disease in an immunocompromised patient with a travel history to Mallorca]. Internist (Berl). 2007;48:727-30 pubmed
    ..Surprisingly, histological examination of the resected colon reveiled the presence of an immunoblastic B-cell lymphoma. In this case, immunosuppression was a prerequisite for the manifestation of leishmaniosis. ..
  19. Al Dujaili E, Kenyon C, Nicol M, Mason J. Liquorice and glycyrrhetinic acid increase DHEA and deoxycorticosterone levels in vivo and in vitro by inhibiting adrenal SULT2A1 activity. Mol Cell Endocrinol. 2011;336:102-9 pubmed publisher
    ..This effect may contribute to the mineralocorticoid actions of glycyrrhetinic acid and gives substance to claims that liquorice also has androgenic properties. ..
  20. Dias Peixoto M, Ferreira A, Almeida P, Braga V, Coutinho D, Melo D, et al. The cardiac expression of Mas receptor is responsive to different physiological and pathological stimuli. Peptides. 2012;35:196-201 pubmed publisher
  21. Schordan S, Grisk O, Schordan E, Miehe B, Rumpel E, Endlich K, et al. OPN deficiency results in severe glomerulosclerosis in uninephrectomized mice. Am J Physiol Renal Physiol. 2013;304:F1458-70 pubmed publisher
    ..WT and OPN knockout mice (OPN-/-) without treatment, after uninephrectomy (UNX), as well as after UNX and desoxycorticosterone acetate (DOCA)-salt treatment with respect to urine parameters, glomerular morphology, and expression of ..
  22. Chan C, Moore J, Budzyn K, Guida E, Diep H, Vinh A, et al. Reversal of vascular macrophage accumulation and hypertension by a CCR2 antagonist in deoxycorticosterone/salt-treated mice. Hypertension. 2012;60:1207-12 pubmed publisher
    ..Hence, our findings highlight CCR2 as a promising therapeutic target to reduce both macrophage accumulation in the vascular wall and blood pressure in hypertension. ..
  23. Imanishi T, Moriwaki C, Hano T, Nishio I. Endothelial progenitor cell senescence is accelerated in both experimental hypertensive rats and patients with essential hypertension. J Hypertens. 2005;23:1831-7 pubmed
    ..The hypertension-induced EPC senescence may affect the process of vascular remodeling. ..
  24. Hilzendeger A, Cassell M, Davis D, Stauss H, Mark A, Grobe J, et al. Angiotensin type 1a receptors in the subfornical organ are required for deoxycorticosterone acetate-salt hypertension. Hypertension. 2013;61:716-22 pubmed publisher
  25. Boini K, Xia M, Xiong J, Li C, Payne L, Li P. Implication of CD38 gene in podocyte epithelial-to-mesenchymal transition and glomerular sclerosis. J Cell Mol Med. 2012;16:1674-85 pubmed publisher
  26. Pietranera L, Saravia F, Gonzalez Deniselle M, Roig P, Lima A, De Nicola A. Abnormalities of the hippocampus are similar in deoxycorticosterone acetate-salt hypertensive rats and spontaneously hypertensive rats. J Neuroendocrinol. 2006;18:466-74 pubmed
    ..Thus, in addition to the deleterious effects of hypertension, endocrine factors may contribute to the abnormalities of hippocampus in SHR and DOCA-treated rats. ..
  27. Vermehren Schmaedick A, Jenkins V, Hsieh H, Brown A, Page M, Brooks V, et al. Upregulation of brain-derived neurotrophic factor expression in nodose ganglia and the lower brainstem of hypertensive rats. J Neurosci Res. 2013;91:220-9 pubmed publisher
    ..A dramatic increase in BDNF in the NG was also detected in DOCA-salt hypertensive rats. Together, our study identifies BDNF as a candidate molecular mediator of activity-dependent changes at baroafferent synapses during hypertension. ..
  28. Wang H, Chen A, Watts S, Galligan J, Fink G. Endothelin in the splanchnic vascular bed of DOCA-salt hypertensive rats. Am J Physiol Heart Circ Physiol. 2005;288:H729-36 pubmed
    ..These results argue against the hypothesis that increased venomotor tone in DOCA-salt hypertension is caused by increased ET-1 concentration around splanchnic venous smooth muscle cells. ..
  29. Vallon V, Huang D, Grahammer F, Wyatt A, Osswald H, Wulff P, et al. SGK1 as a determinant of kidney function and salt intake in response to mineralocorticoid excess. Am J Physiol Regul Integr Comp Physiol. 2005;289:R395-R401 pubmed
    ..6 +/- 0.6 to 5.9 +/- 0.9 ml/day). Thus SGK1 contributes to the stimulation of salt intake, kidney growth, proteinuria, and renal K(+) excretion during mineralocorticoid excess. ..
  30. Benter I, Canatan H, Benboubetra M, Yousif M, Akhtar S. Global upregulation of gene expression associated with renal dysfunction in DOCA-salt-induced hypertensive rats occurs via signaling cascades involving epidermal growth factor receptor: a microarray analysis. Vascul Pharmacol. 2009;51:101-9 pubmed publisher
  31. Chan V, Fenning A, Iyer A, Hoey A, Brown L. Resveratrol improves cardiovascular function in DOCA-salt hypertensive rats. Curr Pharm Biotechnol. 2011;12:429-36 pubmed
    ..These actions of resveratrol could play an important role in the protective effects on the human cardiovascular system reported for this constituent of red wine. ..
  32. Ni W, Fink G, Watts S. The 5-hydroxytryptamine2A receptor is involved in (+)-norfenfluramine-induced arterial contraction and blood pressure increase in deoxycorticosterone acetate-salt hypertension. J Pharmacol Exp Ther. 2007;321:485-91 pubmed
    ..However, it is the 5-HT2A receptor and not the 5-HT2B receptor that participates in these effects...
  33. Lai F, Hsin Y, Huang S, Cheng C, Hsin S, Hsieh M, et al. Down-regulation of adrenal neuronal nitric oxide synthase mRNAs and proteins after deoxycorticosterone acetate-salt treatment in rats. J Steroid Biochem Mol Biol. 2006;101:197-203 pubmed
    ..7-fold down-regulated after DOCA-salt treatment. Our results indicated that the down-regulation of adrenal nNOS synthesis might be associated with the inactivation of adrenal function in face of volume expansion. ..
  34. Ruan C, Ma Y, Ge Q, Li Y, Zhu L, Zhang Y, et al. Complement-mediated inhibition of adiponectin regulates perivascular inflammation and vascular injury in hypertension. FASEB J. 2017;31:1120-1129 pubmed publisher
    ..study, we demonstrated that down-regulation of APN was associated with complement activation in the PVAT of desoxycorticosterone acetate (DOCA)-salt hypertensive mice...
  35. Aceves Ramos A, Valdez R, Gaona B, Willms K, Romano M. Steroid synthesis by Taenia crassiceps WFU cysticerci is regulated by enzyme inhibitors. Gen Comp Endocrinol. 2013;188:212-7 pubmed publisher
    ..We raise the possibility that these drug actions may be beneficially. ..
  36. Artunc F, Amann K, Nasir O, Friedrich B, Sandulache D, Jahovic N, et al. Blunted DOCA/high salt induced albuminuria and renal tubulointerstitial damage in gene-targeted mice lacking SGK1. J Mol Med (Berl). 2006;84:737-46 pubmed
    ..this end, SGK1-knockout mice (sgk1 (-/-)) and their wild-type littermates (sgk1 (+/+)) were implanted with desoxycorticosterone acetate (DOCA)-release pellets and offered 1% saline as drinking water for 12 weeks...
  37. Pérez Rivera A, Fink G, Galligan J. Alpha-1B adrenoceptors mediate neurogenic constriction in mesenteric arteries of normotensive and DOCA-salt hypertensive mice. Auton Neurosci. 2005;121:64-73 pubmed
    ..Nerve-released NE acts primarily at alpha1B-and to a lesser extent at alpha1A-ARs in SHAM arteries whereas NE mediates neurogenic constrictions in DOCA-salt arteries by acting at alpha1B-ARs. ..
  38. Carreño J, Verdugo F, Contreras F, Montellano F, Veloso S, Schalper K, et al. Spironolactone inhibits the activity of the Na+/H+ exchanger in the aorta of mineralocorticoid-induced hypertensive rats. J Renin Angiotensin Aldosterone Syst. 2015;16:1225-31 pubmed publisher
    ..Uninephrectomized male Sprague-Dawley rats received subcutaneously 10 mg/week of desoxycorticosterone (DOCA) with or without 20 mg/kg of spironolactone, or vehicle alone (n = 20)...
  39. Zheleznova N, Sedelnikova A, Weiss D. alpha1beta2delta, a silent GABAA receptor: recruitment by tracazolate and neurosteroids. Br J Pharmacol. 2008;153:1062-71 pubmed publisher
    ..In the presence of tracazolate or endogenous neurosteroids however, this particular receptor isoform could exert a profound inhibitory influence on neuronal activity. ..
  40. Storey E, Kaufman S. Effect of pregnancy and 5alpha-pregnan-3alpha-ol-20-one on atrial receptor afferent discharge in rats. Am J Physiol Regul Integr Comp Physiol. 2004;287:R1427-33 pubmed
    ..This effect may be mimicked by chronic, but not acute, pregnan. We propose that, during pregnancy, pregnan alters the transducer properties of the atrial volume receptors, thus allowing blood volume to increase. ..
  41. Li X, Woodard G, Brown J, Rosado J. Renal atrial natriuretic peptide receptors binding properties and function are resistant to DOCA-salt-induced hypertension in rats. Regul Pept. 2006;137:114-20 pubmed
    ..These findings indicate that NPR-A and NPR-C binding properties and NPR-C-mediated inhibition of cAMP generation remain unaltered in DOCA-treated rats. ..
  42. Hosie A, Clarke L, da Silva H, Smart T. Conserved site for neurosteroid modulation of GABA A receptors. Neuropharmacology. 2009;56:149-54 pubmed publisher
  43. Morris M, Na E, Johnson A. Mineralocorticoid receptor antagonism prevents hedonic deficits induced by a chronic sodium appetite. Behav Neurosci. 2010;124:211-24 pubmed publisher
    ..We conclude that an unresolved sodium appetite will reduce responding for rewards and that experimental manipulations that reduce sodium appetite (e.g., access to saline or blockade of MR) decrease hedonic deficits. ..
  44. Stancu E, Braun Falco M, Bruckner Tuderman L, Schempp C. [Umbilicated blisters on sun-exposed skin]. Hautarzt. 2007;58:343-6 pubmed
  45. Scimemi A, Andersson A, Heeroma J, Strandberg J, Rydenhag B, McEvoy A, et al. Tonic GABA(A) receptor-mediated currents in human brain. Eur J Neurosci. 2006;24:1157-60 pubmed
    ..These tonic currents have cell type-specific pharmacologies, opening up the possibility of targeted therapeutics. ..
  46. Galligan J, Miller S, Katki K, Supowit S, Dipette D, Fink G. Increased substance P content in nerve fibers associated with mesenteric veins from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Regul Pept. 2006;133:97-104 pubmed
    ..NK-3 receptors mediate venoconstriction which is unchanged in DOCA-salt hypertension. Increased release of SP from perivenous nerves might contribute to the increased venomotor tone in DOCA-salt hypertension. ..
  47. Zhang A, Jia Z, Wang N, Tidwell T, Yang T. Relative contributions of mitochondria and NADPH oxidase to deoxycorticosterone acetate-salt hypertension in mice. Kidney Int. 2011;80:51-60 pubmed publisher
    ..Thus, the mitochondrial respiratory chain is a major source of oxidative stress in DOCA-salt hypertension, whereas NADPH oxidase may have a relatively minor role during the early stage of hypertension. ..
  48. Ni W, Lookingland K, Watts S. Arterial 5-hydroxytryptamine transporter function is impaired in deoxycorticosterone acetate and Nomega-nitro-L-arginine but not spontaneously hypertensive rats. Hypertension. 2006;48:134-40 pubmed
    ..Our study suggested that an altered serotonergic system by impaired 5-HTT function might play a role in blood pressure regulation in DOCA-salt and LNNA-hypertensive rats. ..
  49. Bartlett C, Boyd K, Harris R, Zent R, Breyer R. EP1 disruption attenuates end-organ damage in a mouse model of hypertension. Hypertension. 2012;60:1184-91 pubmed publisher
    ..Thus, reduction in blood pressure by disruption of EP1 reduced incidence of mortality and decreased organ damage, suggesting that EP1 receptor blockade may be a viable target for antihypertensive therapy. ..
  50. Wang Y, Wang D. Aggravated renal inflammatory responses in TRPV1 gene knockout mice subjected to DOCA-salt hypertension. Am J Physiol Renal Physiol. 2009;297:F1550-9 pubmed publisher
  51. Kaufman K, Tanchuck M, Strong M, Finn D. Replacement with GABAergic steroid precursors restores the acute ethanol withdrawal profile in adrenalectomy/gonadectomy mice. Neuroscience. 2010;166:5-14 pubmed publisher
    ..These findings indicate that the increase in acute withdrawal severity after ADX/GDX may be due to the loss of GABAergic NAS, providing insight into the contribution of endogenous GABAergic NAS to ethanol withdrawal severity...
  52. Yao B, Harris R, Zhang M. Intrarenal dopamine attenuates deoxycorticosterone acetate/high salt-induced blood pressure elevation in part through activation of a medullary cyclooxygenase 2 pathway. Hypertension. 2009;54:1077-83 pubmed publisher
  53. Leelahavanichkul A, Yan Q, Hu X, Eisner C, Huang Y, Chen R, et al. Angiotensin II overcomes strain-dependent resistance of rapid CKD progression in a new remnant kidney mouse model. Kidney Int. 2010;78:1136-53 pubmed publisher
    ..Thus, reducing renal mass in CD-1 or 129S3 mice mimics many features of human CKD. Angiotensin II can convert the C57BL/6 strain from CKD resistant to susceptible in this disease model. ..