ECE2021 Audio Eposter Presentations Adrenal and Cardiovascular Endocrinology (80 abstracts)
Zona glomerulosa derived Klotho does not regulate aldosterone synthesis in young mice
Cong Tang 1 , Ye Xie 1 , Alessia Scapin 1 , Dominique Loffing 2 , David Breault 3 , Johannes Loffing 2 & Felix Beuschlein 1
1University Hospital Zurich (USZ) and University of Zurich (UZH), Department of Endocrinology, Diabetology and Clinical Nutrition, Switzerland; 2University of Zurich (UZH), Institute of Anatomy, Switzerland; 3Boston Children’s Hospital, Division of Endocrinology, United States
Klotho (Kl), initially identified as an antiaging gene, plays a critical role in the regulation of renal and adrenal dependent fluid homeostasis. A previous study reported that haplodeficiency of Kl in mice resulted in increased aldosterone synthase (CYP11B2) expression, elevated plasma aldosterone and high blood pressure. This phenotype was presumed to result from diminished Kl expression in zona glomerulosa (zG) of the adrenal. To examine whether Kl expressed in zG is indeed a critical regulator of aldosterone synthesis, we generated a tamoxifen-inducible, zG-specific mouse model of KI deficiency by crossing Kl-flox mice with Cyp11b2-CreERT mice (zG-Kl). Tamoxifen-treated Cyp11b2-CreERT animals (zG-Cre) served as controls. Rosa26-mTmG reporter mice were used for Cre-dependent lineage-marking. Two weeks after tamoxifen induction, the specificity of the zG-Cre line was verified using immunofluorescence analysis to show that GFP expression was restricted to the zG. RNAScope in situ hybridization revealed a 65% down-regulation of Kl mRNA expression in zG of zG-Kl mice at 12-weeks of age compared to control mice. Despite this, zG-Kl mice exhibited no difference in adrenal Cyp11b2 expression or plasma aldosterone levels compared to control mice independent of sex. These results suggest that zG-derived Kl per se does not significantly regulate aldosterone synthesis in young adult mice. Further studies are required to investigate the role of adrenal Kl in aldosterone synthesis in aged mice.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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