Identification of genes with altered expression in male and female Schlager hypertensive mice

BMC Medical Genetics

Joanne M Lind²  Geoffrey A Head¹  Nicole Steiner²  Nerissa L Hearn²  Kristy L Jackson¹  Christine L Chiu² 

[1] Department of Pharmacology, Monash University, Victoria, Australia;School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith 2751, NSW, Australia

关键词: Genome wide gene expression;    Schlager mouse;   

Others  :  1090843
DOI  :  10.1186/s12881-014-0101-x

 received in 2014-02-19, accepted in 2014-08-19,  发布年份 2014

【 摘 要 】

Background

Numerous studies have shown sex differences in the onset and severity of hypertension. Despite these sex-differences the majority of animal studies are carried out in males. This study investigated expression changes in both male and female hypertensive mouse kidneys to identify common mechanisms that may be involved in the development of hypertension.

Methods

The Schlager hypertensive mouse model (BPH/2J) and its normotensive control (BPN/3J) were used in this study. Radiotelemetry was performed on 12 to 13 week old BPH/2J and BPN/3J male and female animals. Affymetrix GeneChip Mouse Gene 1.0 ST Arrays were performed in kidney tissue from 12 week old BPH/2J and BPN/3J male and female mice (n = 6/group). Genes that were differentially expressed in both male and female datasets were validated using qPCR.

Results

Systolic arterial pressure and heart rate was significantly higher in BPH/2J mice compared with BPN/3J mice in both males and females. Microarray analysis identified 153 differentially expressed genes that were common between males and females (70 upregulated and 83 downregulated). We validated 15 genes by qPCR. Genes involved in sympathetic activity (Hdc, Cndp2), vascular ageing (Edn3), and telomere maintenance (Mcm6) were identified as being differentially expressed between BPH/2J and BPN/3J comparisons. Many of these genes also exhibited expression differences between males and females within a strain.

Conclusions

This study utilised data from both male and female animals to identify a number of genes that may be involved in the development of hypertension. We show that female data can be used to refine candidate genes and pathways, as well as highlight potential mechanisms to explain the differences in prevalence and severity of disease between men and women.

【 授权许可】

   
2014 Chiu et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Chen YF: Sexual dimorphism of hypertension. Curr Opin Nephrol Hypertens 1996, 5(2):181-185.
• [2]Marques FZ, Campain AE, Davern PJ, Yang YH, Head GA, Morris BJ: Global identification of the genes and pathways differentially expressed in hypothalamus in early and established neurogenic hypertension. Physiol Genomics 2011, 43(12):766-771.
• [3]Puig O, Wang IM, Cheng P, Zhou P, Roy S, Cully D, Peters M, Benita Y, Thompson J, Cai TQ: Transcriptome profiling and network analysis of genetically hypertensive mice identifies potential pharmacological targets of hypertension. Physiol Genomics 2010, 42A(1):24-32.
• [4]Davern PJ, Nguyen-Huu TP, La Greca L, Abdelkader A, Head GA: Role of the sympathetic nervous system in Schlager genetically hypertensive mice. Hypertension 2009, 54(4):852-859.
• [5]Jackson KL, Marques FZ, Watson AM, Palma-Rigo K, Nguyen-Huu TP, Morris BJ, Charchar FJ, Davern PJ, Head GA: A novel interaction between sympathetic overactivity and aberrant regulation of renin by miR-181a in BPH/2J genetically hypertensive mice. Hypertension 2013, 62(4):775-781.
• [6]Chiu CL, Morgan CT, Lupton SJ, Lind JM: Parent of origin influences the cardiac expression of vascular endothelial growth factor (Vegfa).BMC Med Genet 2013, 14:43.
• [7]Tabas-Madrid D, Nogales-Cadenas R, Pascual-Montano A: GeneCodis3: a non-redundant and modular enrichment analysis tool for functional genomics. Nucleic Acids Res 2012, 40(Web Server issue):W478-W483.
• [8]Carmona-Saez P, Chagoyen M, Tirado F, Carazo JM, Pascual-Montano A: GENECODIS: a web-based tool for finding significant concurrent annotations in gene lists.Genome Biol 2007, 8(1):R3.
• [9]Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F: Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes.Genome Biol 2002, 3(7):RESEARCH0034.
• [10]Katoh Y, Katoh M: Comparative integromics on Angiopoietin family members. Int J Mol Med 2006, 17(6):1145-1149.
• [11]Comes N, Buie LK, Borras T: Evidence for a role of angiopoietin-like 7 (ANGPTL7) in extracellular matrix formation of the human trabecular meshwork: implications for glaucoma. Genes Cells 2011, 16(2):243-259.
• [12]Newman-Casey PA, Talwar N, Nan B, Musch DC, Stein JD: The relationship between components of metabolic syndrome and open-angle glaucoma. Ophthalmology 2011, 118(7):1318-1326.
• [13]Riedl E, Pfister F, Braunagel M, Brinkkotter P, Sternik P, Deinzer M, Bakker SJ, Henning RH, van den Born J, Kramer BK, Navis G, Hammes HP, Yard B, Koeppel H: Carnosine prevents apoptosis of glomerular cells and podocyte loss in STZ diabetic rats. Cell Physiol Biochem 2011, 28(2):279-288.
• [14]Niijima A, Okui T, Matsumura Y, Yamano T, Tsuruoka N, Kiso Y, Nagai K: Effects of L-carnosine on renal sympathetic nerve activity and DOCA-salt hypertension in rats. Auton Neurosci 2002, 97(2):99-102.
• [15]Willi SM, Zhang Y, Hill JB, Phelan MC, Michaelis RC, Holden KR: A deletion in the long arm of chromosome 18 in a child with serum carnosinase deficiency. Pediatr Res 1997, 41(2):210-213.
• [16]Tanida M, Kaneko H, Shen J, Nagai K: Involvement of the histaminergic system in renal sympathetic and cardiovascular responses to leptin and ghrelin. Neurosci Lett 2007, 413(1):88-92.
• [17]Morgan TK, Montgomery K, Mason V, West RB, Wang L, van de Rijn M, Higgins JP: Upregulation of histidine decarboxylase expression in superficial cortical nephrons during pregnancy in mice and women. Kidney Int 2006, 70(2):306-314.
• [18]You Z, Komamura Y, Ishimi Y: Biochemical analysis of the intrinsic Mcm4-Mcm6-Mcm7 DNA helicase activity. Mol Cell Biol 1999, 19(12):8003-8015.
• [19]Chai W, Zheng L, Shen B: DNA2, a new player in telomere maintenance and tumor suppression. Cell Cycle 2013, 12(13):1985-1986.
• [20]Lin W, Sampathi S, Dai H, Liu C, Zhou M, Hu J, Huang Q, Campbell J, Shin-Ya K, Zheng L, Chai W, Shen B: Mammalian DNA2 helicase/nuclease cleaves G-quadruplex DNA and is required for telomere integrity. EMBO J 2013, 32(10):1425-1439.
• [21]Ungar L, Yosef N, Sela Y, Sharan R, Ruppin E, Kupiec M: A genome-wide screen for essential yeast genes that affect telomere length maintenance. Nucleic Acids Res 2009, 37(12):3840-3849.
• [22]Fuster JJ, Diez J, Andres V: Telomere dysfunction in hypertension. J Hypertens 2007, 25(11):2185-2192.
• [23]Levy D, Ehret GB, Rice K, Verwoert GC, Launer LJ, Dehghan A, Glazer NL, Morrison AC, Johnson AD, Aspelund T, Aulchenko Y, Lumley T, Köttgen A, Vasan RS, Rivadeneira F, Eiriksdottir G, Guo X, Arking DE, Mitchell GF, Mattace-Raso FU, Smith AV, Taylor K, Scharpf RB, Hwang SJ, Sijbrands EJ, Bis J, Harris TB, Ganesh SK, O'Donnell CJ, Hofman A: Genome-wide association study of blood pressure and hypertension. Nat Genet 2009, 41(6):677-687.
• [24]Lattmann T, Shaw S, Munter K, Vetter W, Barton M: Anatomically distinct activation of endothelin-3 and the L-arginine/nitric oxide pathway in the kidney with advanced aging. Biochem Biophys Res Commun 2005, 327(1):234-241.
• [25]Ostchega Y, Dillon CF, Hughes JP, Carroll M, Yoon S: Trends in hypertension prevalence, awareness, treatment, and control in older U.S. adults: data from the National Health and Nutrition Examination Survey 1988 to 2004. J Am Geriatr Soc 2007, 55(7):1056-1065.
• [26]Fiorentino DF, Zlotnik A, Vieira P, Mosmann TR, Howard M, Moore KW, O’Garra A: IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol 1991, 146(10):3444-3451.
• [27]Park HK, Kim DH, Yun DH, Ban JY: Association between IL10, IL10RA, and IL10RB SNPs and ischemic stroke with hypertension in Korean population. Mol Biol Rep 2013, 40(2):1785-1790.
• [28]Kalkunte S, Nevers T, Norris WE, Sharma S: Vascular IL-10: a protective role in preeclampsia. J Reprod Immunol 2011, 88(2):165-169.
• [29]Orange S, Horvath J, Hennessy A: Preeclampsia is associated with a reduced interleukin-10 production from peripheral blood mononuclear cells. Hypertens Pregnancy 2003, 22(1):1-8.