Abstract 568: Congenic Mapping of Hypertension in the Nephrectomy Model of Chronic Kidney Disease.

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Sylvia Cechova ◽  
Rosa Chan ◽  
Christine Rudy ◽  
Thu H Le

Introduction: We previously reported a locus on mouse chromosome 11 (chrom 11) linked to development of hypertension (HTN) after sub-total nephrectomy (Nx). To begin fine mapping, we used the 129S6 (129) susceptible strain and the C57BL/6 (B6) resistant strain to generate 4 reciprocal congenic lines carrying ~ 2-LOD intervals of the linked locus for recombinant progeny testing. The intervals are defined by microsatellite markers 1-5 and markers 1-6, corresponding to regions defined by markers D11Mit2 and D11Mit177, and D11Mit2 and D11Mit285, respectively. Through brother-sister matings, the 4 lines are as follows: 1) 129 background, homozygous for B6 segment defined by markers 1-5 (129 Chrom11:1-5ofB6 ), 2) 129 background, homozygous for 129 segment defined by markers 1-5 (129 Chrom11:1-5of129 ), 3) B6 background, homozygous for 129 segment defined by markers 1-6 (B6 Chrom11:1-6of129 ) and 4) B6 background, homozygous for B6 segment defined by markers 1-6 (B6 Chrom11:1-6ofB6 ). Methods: Sub-total Nx was performed on male and female congenic mice at ~ 8 weeks of age. Beginning 4 weeks after surgery, using tail cuff manometer, mice were trained for 2 weeks, after which systolic blood pressure (SBP) was recorded daily for 2 weeks. Results: Table 1 summarizes the average SBP of the congenic lines. Conclusion: These findings confirm the effect of this chrom 11 region is dependent on the 129 genetic background, and suggest that interactions between this 129 locus and other loci in the 129 genome are necessary for the development of HTN after nephron mass reduction. Moreover, the influence of this region on chrom 11 appears to be dependent on sex.

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 424
Author(s):  
Perla Y. Gutiérrez-Arzapalo ◽  
Pilar Rodríguez-Rodríguez ◽  
David Ramiro-Cortijo ◽  
Marta Gil-Ortega ◽  
Beatriz Somoza ◽  
...  

Fetal undernutrition programs hypertension and cardiovascular diseases, and resistance artery remodeling may be a contributing factor. We aimed to assess if fetal undernutrition induces resistance artery remodeling and the relationship with hypertension. Sprague–Dawley dams were fed ad libitum (Control) or with 50% of control intake between days 11 and 21 of gestation (maternal undernutrition, MUN). In six-month-old male and female offspring we assessed blood pressure (anesthetized and tail-cuff); mesenteric resistance artery (MRA) structure and mechanics (pressure myography), cellular and internal elastic lamina (IEL) organization (confocal microscopy) and plasma MMP-2 and MMP-9 activity (zymography). Systolic blood pressure (SBP, tail-cuff) and plasma MMP activity were assessed in 18-month-old rats. At the age of six months MUN males exhibited significantly higher blood pressure (anesthetized or tail-cuff) and plasma MMP-9 activity, while MUN females did not exhibit significant differences, compared to sex-matched controls. MRA from 6-month-old MUN males and females showed a smaller diameter, reduced adventitial, smooth muscle cell density and IEL fenestra area, and a leftward shift of stress-strain curves. At the age of eighteen months SBP and MMP-9 activity were higher in both MUN males and females, compared to sex-matched controls. These data suggest that fetal undernutrition induces MRA inward eutrophic remodeling and stiffness in both sexes, independent of blood pressure level. Resistance artery structural and mechanical alterations can participate in the development of hypertension in aged females and may contribute to adverse cardiovascular events associated with low birth weight in both sexes.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jia Y. Wan ◽  
Deborah L. Goodman ◽  
Emileigh L. Willems ◽  
Alexis R. Freedland ◽  
Trina M. Norden-Krichmar ◽  
...  

Abstract Background To identify genetic associations of quantitative metabolic syndrome (MetS) traits and characterize heterogeneity across ethnic groups. Methods Data was collected from GENetics of Noninsulin dependent Diabetes Mellitus (GENNID), a multiethnic resource of Type 2 diabetic families and included 1520 subjects in 259 African-American, European-American, Japanese-Americans, and Mexican-American families. We focused on eight MetS traits: weight, waist circumference, systolic and diastolic blood pressure, high-density lipoprotein, triglycerides, fasting glucose, and insulin. Using genotyped and imputed data from Illumina’s Multiethnic array, we conducted genome-wide association analyses with linear mixed models for all ethnicities, except for the smaller Japanese-American group, where we used additive genetic models with gene-dropping. Results Findings included ethnic-specific genetic associations and heterogeneity across ethnicities. Most significant associations were outside our candidate linkage regions and were coincident within a gene or intergenic region, with two exceptions in European-American families: (a) within previously identified linkage region on chromosome 2, two significant GLI2-TFCP2L1 associations with weight, and (b) one chromosome 11 variant near CADM1-LINC00900 with pleiotropic blood pressure effects. Conclusions This multiethnic family study found genetic heterogeneity and coincident associations (with one case of pleiotropy), highlighting the importance of including diverse populations in genetic research and illustrating the complex genetic architecture underlying MetS.


Genetics ◽  
2002 ◽  
Vol 161 (4) ◽  
pp. 1651-1659 ◽  
Author(s):  
Elena de la Casa-Esperón ◽  
J Concepción Loredo-Osti ◽  
Fernando Pardo-Manuel de Villena ◽  
Tammi L Briscoe ◽  
Jan Michel Malette ◽  
...  

AbstractWe observed that maternal meiotic drive favoring the inheritance of DDK alleles at the Om locus on mouse chromosome 11 was correlated with the X chromosome inactivation phenotype of (C57BL/ 6-Pgk1a × DDK)F1 mothers. The basis for this unexpected observation appears to lie in the well-documented effect of recombination on meiotic drive that results from nonrandom segregation of chromosomes. Our analysis of genome-wide levels of meiotic recombination in females that vary in their X-inactivation phenotype indicates that an allelic difference at an X-linked locus is responsible for modulating levels of recombination in oocytes.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chao-Sheng Lo ◽  
Kana N. Miyata ◽  
Shuiling Zhao ◽  
Anindya Ghosh ◽  
Shiao-Ying Chang ◽  
...  

Abstract We reported previously that overexpression of heterogeneous nuclear ribonucleoprotein F (Hnrnpf) in renal proximal tubular cells (RPTCs) suppresses angiotensinogen (Agt) expression, and attenuates systemic hypertension and renal injury in diabetic Hnrnpf-transgenic (Tg) mice. We thus hypothesized that deletion of Hnrnpf in the renal proximal tubules (RPT) of mice would worsen systemic hypertension and kidney injury, perhaps revealing novel mechanism(s). Tubule-specific Hnrnpf knockout (KO) mice were generated by crossbreeding Pax8-Cre mice with floxed Hnrnpf mice on a C57BL/6 background. Both male and female KO mice exhibited elevated systolic blood pressure, increased urinary albumin/creatinine ratio, tubulo-interstitial fibrosis and glycosuria without changes in blood glucose or glomerular filtration rate compared with control littermates. However, glycosuria disappeared in male KO mice at the age of 12 weeks, while female KO mice had persistent glycosuria. Agt expression was elevated, whereas sodium-glucose co-transporter 2 (Sglt2) expression was down-regulated in RPTs of both male and female KO mice as compared to control littermates. In vitro, KO of HNRNPF in human RPTCs (HK-2) by CRISPR gRNA up-regulated AGT and down-regulated SGLT2 expression. The Sglt2 inhibitor canagliflozin treatment had no effect on Agt and Sglt2 expression in HK-2 and in RPTCs of wild-type mice but induced glycosuria. Our results demonstrate that Hnrnpf plays a role in the development of hypertension and glycosuria through modulation of renal Agt and Sglt2 expression in mice, respectively.


2005 ◽  
Vol 10 (1) ◽  
pp. 42-47 ◽  
Author(s):  
Utako Umemura ◽  
Mako Ishimori ◽  
Toshio Kobayashi ◽  
Yuji Tamura ◽  
Kazuko A. Koike ◽  
...  

1996 ◽  
Vol 7 (2) ◽  
pp. 163-163
Author(s):  
G. C. Voss ◽  
H. Jockusch

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