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

Biomolecules. 2021 Apr 20;11(4):609. doi: 10.3390/biom11040609.

Abstract

This study aimed to explore morphology changes in the kidneys of Dab1-/- (yotari) 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 Dab1 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 yotari 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 yotari 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 yotari 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 yotari.

Keywords: immunofluorescence staining; kidney function; postnatal kidney development; transmission electron microscopy; yotari.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Genes, Recessive
  • Homozygote
  • Kidney Cortex / metabolism
  • Kidney Cortex / ultrastructure
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Nephrons / metabolism
  • Nephrons / ultrastructure
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Phenotype*
  • Receptor, Notch2 / genetics
  • Receptor, Notch2 / metabolism
  • Reelin Protein
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Urogenital Abnormalities / genetics*
  • Urogenital Abnormalities / metabolism
  • Urogenital Abnormalities / pathology
  • Vesico-Ureteral Reflux / genetics*
  • Vesico-Ureteral Reflux / metabolism
  • Vesico-Ureteral Reflux / pathology

Substances

  • Cell Adhesion Molecules, Neuronal
  • Dab1 protein, mouse
  • Extracellular Matrix Proteins
  • Map1lc3b protein, mouse
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Notch2 protein, mouse
  • Receptor, Notch2
  • Reelin Protein
  • Reln protein, mouse
  • Serine Endopeptidases
  • Casp3 protein, mouse
  • Caspase 3

Supplementary concepts

  • Cakut