A Homozygous Dab1<sup>−/−</sup> Is a Potential Novel Cause of Autosomal Recessive Congenital Anomalies of the Mice Kidney and Urinary Tract

This study aimed to explore morphology changes in the kidneys of <i>Dab1<sup>−/−</sup></i> (<i>yotari)</i> mice, as well as expression patterns of reelin, NOTCH2, LC3B, and cleaved caspase3 (CASP3) proteins, as potential determinants of normal kidney formation and...

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Main Authors: Anita Racetin, Natalija Filipović, Mirela Lozić, Masaki Ogata, Larissa Gudelj Ensor, Nela Kelam, Petra Kovačević, Koichiro Watanabe, Yu Katsuyama, Mirna Saraga-Babić, Merica Glavina Durdov, Katarina Vukojević
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/11/4/609
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Summary:This study aimed to explore morphology changes in the kidneys of <i>Dab1<sup>−/−</sup></i> (<i>yotari)</i> mice, as well as expression patterns of reelin, NOTCH2, LC3B, and cleaved caspase3 (CASP3) proteins, as potential determinants of normal kidney formation and function. We assumed that <i>Dab1</i> functional inactivation may cause disorder in a wide spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). Animals were sacrificed at postnatal days P4, P11, and P14. Paraffin-embedded kidney tissues were sectioned and analyzed by immunohistochemistry using specific antibodies. Kidney specimens were examined by bright-field, fluorescence, and electron microscopy. Data were analyzed by two-way ANOVA and t-tests. We noticed that <i>yotari</i> kidneys were smaller in size with a reduced diameter of nephron segments and thinner cortex. TEM microphotographs revealed foot process effacement in the glomeruli (G) of <i>yotari</i> mice, whereas aberrations in the structure of proximal convoluted tubules (PCT) and distal convoluted tubules (DCT) were not observed. A significant increase in reelin expression, NOTCH2, LC3B and cleaved CASP3 proteins was observed in the glomeruli of <i>yotari</i> mice. Renal hypoplasia in conjunction with foot process effacement and elevation in the expression of examined proteins in the glomeruli revealed CAKUT phenotype and loss of functional kidney tissue of <i>yotari.</i>
ISSN:2218-273X