Genetic deletion of connexin 37 causes polyuria and polydipsia

Xue, Jianxiang; Thomas, Linto; Rieg, Jessica A Dominguez; Fenton, Robert A.; Rieg, Timo

doi:10.1371/journal.pone.0244251

Cited by 3 publications

(2 citation statements)

References 79 publications

(102 reference statements)

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“…The latter finding might be associated with vascular development, since Cx37 is involved in different vascular pathologies [31]. Mice with Cx37 dab1−/− showed problems with body water handling via the kidneys, resulting in polyuria and polydipsia [32]. In addition, Cx40 displayed a more specific pattern in human samples and was expressed mostly in the capillary network.…”

Section: Discussionmentioning

confidence: 98%

The Interplay of Cx26, Cx32, Cx37, Cx40, Cx43, Cx45, and Panx1 in Inner-Ear Development of Yotari (dab1−/−) Mice and Humans

et al. 2022

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We investigated DAB1-protein deficiency in the inner-ear development of yotari in comparison to humans and wild-type (wt) mice by immunofluorescence for the expression of connexins (Cxs) and the pannexin Panx1. The spatial and temporal dynamics of Cx26, Cx32, Cx37, Cx40, Cx43, Cx45, and Panx1 were determined in the sixth and eighth weeks of human development and at the corresponding mouse embryonic E13.5 and E15.5, in order to examine gap junction intercellular communication (GJIC) and hemichannel formation. The quantification of the area percentage covered by positive signal was performed for the epithelium and mesenchyme of the cochlear and semicircular ducts and is expressed as the mean ± SD. The data were analysed by one-way ANOVA. Almost all of the examined Cxs were significantly decreased in the cochlear and semicircular ducts of yotari compared to wt and humans, except for Cx32, which was significantly higher in yotari. Cx40 dominated in human inner-ear development, while yotari and wt had decreased expression. The Panx1 expression in yotari was significantly lower than that in the wt and human inner ear, except at E13.5 in the mesenchyme of the wt and epithelium and mesenchyme of humans. Our results emphasize the relevance of GJIC during the development of vestibular and cochlear functions, where they can serve as potential therapeutic targets in inner-ear impairments.

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Section: Discussionmentioning

confidence: 98%

The Interplay of Cx26, Cx32, Cx37, Cx40, Cx43, Cx45, and Panx1 in Inner-Ear Development of Yotari (dab1−/−) Mice and Humans

et al. 2022

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“…Стимуляция рениновой системы с помощью ИАПФ в сочетании с диетой с низким содержанием соли значительно увеличивает экспрессию Cx 37. В то же время, мыши Cx 37 -/имеют более высокое потребление жидкости и более низкую осмоляльность мочи [29]. Таким образом, можно предположить, что Cx 37 участвует в функциональной адаптации канальцевого транспорта в ответ на изменения солевой нагрузки.…”

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Clinical Aspects of Connexins 37, 40, 43, 45 Expression in the Embryonic and Adult Kidneys

Shapovalova,

Kutuzova,

Vasilenko

et al. 2023

Žurnal anatomii i gistopatologii

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Nowdays, there is a wide variety of judgments regarding the specific expression of some forms of connexins (Cx) in the renin apparatus of the embryonic and adult kidneys. Establishing the exact intrarenal localization of Cx 40, 37, 43, 45 is a prerequisite for understanding their functional role in normal renal organogenesis, as well as in maintaining fluid homeostasis and controlling renin secretion. At 8–10 weeks of embryonic development, the expression of various Cx is observed in the epithelium of blood vessels and renal tubules, as well as in the region of the renal renin apparatus, but with different patterns of expression and intensity over time. During embryogenesis, the expression of Cx 40 is higher than that of Cx 43, 37, and 45. In the postnatal period, the expression of Cx 40 decreases, while the expression of others increases. Cx 40 is involved in the formation of the renin apparatus in the developing kidney, while Cx 37, Cx 43, and Cx 45 are involved in signaling important for postnatal maintenance of kidney function and blood pressure control. Knockout Cx 45 is a lethal mutation that leads to impaired differentiation of smooth muscle tissue of arterioles. On the contrary, the deletion of individual genes Cx 37, 40 and 43 has little effect on renal organogenesis, probably due to the redundancy and interchangeability of various connexin isoforms. Experimental studies in the adult kidney demonstrate that arterial endothelial cells express Cx 40 and Cx 37 and, to a lesser extent, Cx 43, while smooth muscle cells express Cx 45. The cells of the renin apparatus are characterized by the expression of Cx 37, Cx 40, Cx 43 and Cx 45, with the highest content of Cx 40, especially in juxtaglomerular cells. Adequate and coordinated work of Cx is crucial for the regulation of renal hemodynamics and renin secretion in nephrology. The use of specific connexin-mimetic peptides may lead to the development of more effective methods for controlling renin secretion.

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NHE3 in the thick ascending limb is required for sustained but not acute furosemide-induced urinary acidification

Xue

Thomas

Rieg

et al. 2022

American Journal of Physiology-Renal Physiology

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The Na+/H+ exchanger isoform 3 (NHE3) facilitates Na+ reabsorption and H+ secretion by the kidneys. Despite stronger NHE3 abundance in the thick ascending limb (TAL) compared to the S1 and S2 segments of the proximal tubule, the role of NHE3 in the TAL is poorly understood. To investigate the role of NHE3 in the TAL, we generated and phenotyped TAL-specific NHE3 knockout mice (NHE3TAL-KO). Compared to control mice, NHE3TAL-KO mice did not show significant differences in body weight, blood pH or plasma Na+, K+ or Cl- levels. Fluid intake trended to be higher and urine osmolality was significantly lower in NHE3TAL-KO mice. Despite a similar GFR, NHE3TAL-KO mice had a greater urinary K+/creatinine ratio. One proposed role of NHE3 relates to furosemide-induced urinary acidification. Acute bolus treatment with furosemide under anesthesia did not result in differences in the dose dependence of urinary flow rate, Cl- excretion or maximal urinary acidification between genotypes; however, in contrast to control mice, urinary pH returned immediately towards baseline levels in NHE3TAL-KO mice. Chronic furosemide treatment reduced urine osmolality similarly in both genotypes but metabolic alkalosis, hypokalemia and calciuresis were absent in NHE3TAL-KO mice. Compared to vehicle, chronic furosemide treatment in control mice resulted in greater NKCC2 and lower Npt2a abundances, effects that were absent in NHE3TAL-KO mice. In summary, NHE3 in the TAL plays a role for the sustained acidification effect of furosemide. Consistent with this, long-term treatment with furosemide did not result in metabolic alkalosis in NHE3TAL-KO mice.

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Genetic deletion of connexin 37 causes polyuria and polydipsia

Cited by 3 publications

References 79 publications

The Interplay of Cx26, Cx32, Cx37, Cx40, Cx43, Cx45, and Panx1 in Inner-Ear Development of Yotari (dab1−/−) Mice and Humans

The Interplay of Cx26, Cx32, Cx37, Cx40, Cx43, Cx45, and Panx1 in Inner-Ear Development of Yotari (dab1−/−) Mice and Humans

Clinical Aspects of Connexins 37, 40, 43, 45 Expression in the Embryonic and Adult Kidneys

NHE3 in the thick ascending limb is required for sustained but not acute furosemide-induced urinary acidification

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