The spiny mouse (Acomys cahirinus) completes nephrogenesis before birth

The spiny mouse is relatively mature at birth. We hypothesized that like other organs, the kidney may be more developed in the spiny mouse at birth, than in other rodents. If nephrogenesis is complete before birth, the spiny mouse may provide an excellent model with which to study the effects of an altered intrauterine environment on renal development. Due to its desert adaptation, the spiny mouse may have a reduced cortex-to-medulla ratio but an equivalent total nephron number to the C57/BL mouse. Kidneys were collected from fetal and neonatal spiny mice and sectioned for gross examination of metanephric development. Kidneys were collected from adult spiny mice (10 wk of age), and glomerular number, volume, and cortex-to-medulla ratios were determined using unbiased stereology. Nephrogenesis is complete in spiny mouse kidneys before birth. Metanephrogenesis begins at ∼ day 18, and by day 38 of a 40-day gestation, the nephrogenic zone is no longer present. Spiny mice have a significantly ( P < 0.001) lower total nephron number compared with C57/BL mice, although the total glomerular volume is similar. The cortex-to-medulla ratio of the spiny mouse is significantly ( P < 0.01) smaller. The spiny mouse is the first rodent species shown to complete nephrogenesis before birth. This makes it an attractive candidate for the study of fetal and neonatal kidney development and function. The reduced total nephron number and cortex-to-medulla ratio in the spiny mouse may contribute to its ability to highly concentrate its urine under stressful conditions (i.e., dehydration).

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Maternal dexamethasone treatment at midgestation reduces nephron number and alters renal gene expression in the fetal spiny mouse

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00481.2006 ◽

2007 ◽

Vol 292 (1) ◽

pp. R453-R461 ◽

Cited By ~ 72

Author(s):

Hayley Dickinson ◽

David W. Walker ◽

E. Marelyn Wintour ◽

Karen Moritz

Keyword(s):

Blood Pressure ◽

Branching Morphogenesis ◽

Spiny Mouse ◽

Pcr Analysis ◽

Nephron Number ◽

Unbiased Stereology ◽

Expression Of Genes ◽

Basal Blood Pressure ◽

First Time ◽

Nephron Deficit

We investigated the effects of maternal glucocorticoid exposure in the spiny mouse, a precocial species with a relatively long gestation, few offspring, and in which nephrogenesis is complete before birth. We hypothesized that exposure of the fetus to glucocorticoids before the formation of glomeruli would result in adult hypertensive offspring with fewer nephrons. Furthermore, we hypothesized that this nephron deficit would result from changes in expression of genes involved in branching morphogenesis. Osmotic pumps implanted in pregnant spiny mice at midgestation ( day 20) delivered dexamethasone (dex; 125 μg/kg) or saline for 60 h. Females were killed at day 23 of gestation and kidneys were frozen for real-time PCR analysis or allowed to deliver their offspring. At 20 wk of age, blood pressure was measured in the offspring for 1 wk before nephron number was determined using unbiased stereology. Males and females exposed to dex had significantly fewer nephrons (male: saline: 7,870 ± 27, dex: 6,878 ± 173; female: saline: 7,526 ± 62, dex: 5,886 ± 382; P < 0.001) compared with controls. Dex had no effect on basal blood pressure. Fetal kidneys collected at day 23 of gestation from dex-exposed mothers showed increased mRNA expression of BMP4 ( P < 0.05), TGF-β1 ( P < 0.05), genes known to inhibit branching morphogenesis and gremlin ( P < 0.01), an antagonist of BMP4, compared with saline controls. This study shows for the first time an upregulation of branching morphogenic genes in the fetal kidney in a model of excess maternal glucocorticoids that leads to a nephron deficit in the adult. This study also provides evidence that a reduced nephron number does not necessarily lead to development of hypertension.

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Abstract 094: Pappa2 is Important for Determining the Nephron Number

Hypertension ◽

10.1161/hyp.68.suppl_1.094 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Vikash Kumar ◽

Chun Yang ◽

Aron M Geurts ◽

Mingyu Liang ◽

Allen W Cowley

Keyword(s):

Mrna Expression ◽

Kidney Development ◽

Brown Norway ◽

Ureteric Bud ◽

Induced Hypertension ◽

Allele Variant ◽

Rat Strain ◽

Nephron Development ◽

And Function ◽

Igfbp 3

Pappa2 is a metalloproteinase which specifically cleaves IGFBP-3 and IGFBP-5 and in turn releases IGF-1. Recently, we have shown that a subcongenic Dahl salt-sensitive (SS) rat strain containing a 0.71 Mbp of chromosome 13 which includes Pappa2 gene from salt-insensitive Brown Norway (26-P strain) is protected significantly (24 mmHg) from salt-induced hypertension (Cowley et al., 2016). Although it is recognized that Pappa2 modulates development of bone size, cranial cartilage and angiogenesis, its role in kidney development and function is unknown. The present study determined the contribution of Pappa2 to nephron development by comparing SS and 26-P rat strains. It was found that Pappa2 mRNA expression was 5-fold higher in embryonic kidney (day 20.5) of the salt-resistant 26-P rats compared with age-matched SS rats. Pappa2 mRNA expression significantly increased with age of kidney reaching a maximum at postnatal day 5 in both strains. Pappa2 mRNA expression at postnatal day 15 was found to be 9-fold higher in the kidney of 26-P compared with SS strain. Immunohistochemistry studies revealed that Pappa2 co-localized with IGFBP-5 in the ureteric bud indicating that Pappa2 could be important for ureteric branching and nephron endowment. Glomerulus/mm 2 was therefore determined by counting total number of glomeruli in kidney sections from pups starting from P0 to P20. The salt-resistant 26-P congenic strain exhibited significantly greater nephron density 9.03 and 7.07 glo/mm 2 compared to 6.89 and 4.85 glo/mm 2 in SS rat at day P15 and P20, respectively. It appears that the Brown Norway pappa2 allele variant prevents the reduced nephron numbers observed in SS rats and thereby protects these congenic rats from salt-induced hypertension.

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Premature differentiation of nephron progenitor cell and dysregulation of gene pathways critical to kidney development in a model of preterm birth

Scientific Reports ◽

10.1038/s41598-021-00489-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Aleksandra Cwiek ◽

Masako Suzuki ◽

Kimberly deRonde ◽

Mark Conaway ◽

Kevin M. Bennett ◽

...

Keyword(s):

Preterm Birth ◽

Progenitor Cells ◽

Kidney Development ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Neonatal Morbidity ◽

Expression Of Genes ◽

Nephron Progenitor ◽

Lower Expression ◽

Nephrogenic Zone

AbstractPreterm birth is a leading cause of neonatal morbidity. Survivors have a greater risk for kidney dysfunction and hypertension. Little is known about the molecular changes that occur in the kidney of individuals born preterm. Here, we demonstrate that mice delivered two days prior to full term gestation undergo premature cessation of nephrogenesis, resulting in a lower glomerular density. Kidneys from preterm and term groups exhibited differences in gene expression profiles at 20- and 27-days post-conception, including significant differences in the expression of fat-soluble vitamin-related genes. Kidneys of the preterm mice exhibited decreased proportions of endothelial cells and a lower expression of genes promoting angiogenesis compared to the term group. Kidneys from the preterm mice also had altered nephron progenitor subpopulations, early Six2 depletion, and altered Jag1 expression in the nephrogenic zone, consistent with premature differentiation of nephron progenitor cells. In conclusion, preterm birth alone was sufficient to shorten the duration of nephrogenesis and cause premature differentiation of nephron progenitor cells. These candidate genes and pathways may provide targets to improve kidney health in preterm infants.

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The excretory system of young chickens experiencing mercury toxicity—effects on kidney development, morphology, and function

Archives of Environmental Contamination and Toxicology ◽

10.1007/bf02332054 ◽

1978 ◽

Vol 7 (1) ◽

pp. 257-271 ◽

Cited By ~ 8

Author(s):

Patricia Y. Hester ◽

John Brake ◽

Charles V. Sikes ◽

Paul Thaxton ◽

Samuel L. Pardue

Keyword(s):

Kidney Development ◽

Excretory System ◽

Mercury Toxicity ◽

And Function ◽

Toxicity Effects

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Chromatin dynamics in kidney development and function

Cell and Tissue Research ◽

10.1007/s00441-014-1884-y ◽

2014 ◽

Vol 356 (3) ◽

pp. 601-608 ◽

Cited By ~ 8

Author(s):

Wibke Bechtel-Walz ◽

Tobias B. Huber

Keyword(s):

Kidney Development ◽

Chromatin Dynamics ◽

And Function

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Organic anion and cation transporter expression and function during embryonic kidney development and in organ culture models

Kidney International ◽

10.1038/sj.ki.5000170 ◽

2006 ◽

Vol 69 (5) ◽

pp. 837-845 ◽

Cited By ~ 45

Author(s):

D.H. Sweet ◽

S.A. Eraly ◽

D.A. Vaughn ◽

K.T. Bush ◽

S.K. Nigam

Keyword(s):

Organ Culture ◽

Kidney Development ◽

Organic Anion ◽

Culture Models ◽

And Function ◽

Transporter Expression

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SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function

Journal of the American Society of Nephrology ◽

10.1681/asn.2016020131 ◽

2016 ◽

Vol 28 (3) ◽

pp. 981-994 ◽

Cited By ~ 29

Author(s):

Man Li ◽

Yong Li ◽

Olivia Weeks ◽

Vladan Mijatovic ◽

Alexander Teumer ◽

...

Keyword(s):

Large Scale ◽

Kidney Development ◽

And Function ◽

Exome Chip ◽

Chip Analysis

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Ischemic tolerance and cardiac repair in the spiny mouse (Acomys)

npj Regenerative Medicine ◽

10.1038/s41536-021-00188-2 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Tim Koopmans ◽

Henriette van Beijnum ◽

Elke F. Roovers ◽

Antonio Tomasso ◽

Divyanshu Malhotra ◽

...

Keyword(s):

Heart Function ◽

Spiny Mouse ◽

Acute Injury ◽

Heart Research ◽

Murid Rodent ◽

Tissue Properties ◽

Spiny Mice ◽

Heart Repair ◽

Research Findings ◽

Bona Fide

AbstractIschemic heart disease and by extension myocardial infarction is the primary cause of death worldwide, warranting regenerative therapies to restore heart function. Current models of natural heart regeneration are restricted in that they are not of adult mammalian origin, precluding the study of class-specific traits that have emerged throughout evolution, and reducing translatability of research findings to humans. Here, we present the spiny mouse (Acomys spp.), a murid rodent that exhibits bona fide regeneration of the back skin and ear pinna, as a model to study heart repair. By comparing them to ordinary mice (Mus musculus), we show that the acute injury response in spiny mice is similar, but with an associated tolerance to infarction through superior survivability, improved ventricular conduction, and near-absence of pathological remodeling. Critically, spiny mice display increased vascularization, altered scar organization, and a more immature phenotype of cardiomyocytes, with a corresponding improvement in heart function. These findings present new avenues for mammalian heart research by leveraging unique tissue properties of the spiny mouse.

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