Background: ShcA (SHC1) is a phosphotyrosine adaptor protein which plays broad signaling roles within the cell. Systemic loss of ShcA during embryogenesis is lethal, while its aberrant expression contributes to disease. We recently demonstrated that ShcA is highly expressed during glomerular development and that it is upregulated within podocytes in experimental kidney injury and chronic kidney disease. The objective of this study was to analyze the in vivo role of ShcA in podocytes.
Methods: We selectively deleted all three isoforms of ShcA from mouse kidney podocytes using the Cre/lox system driven by the podocyte-specific podocin promoter (Nphs2). Immunostaining of kidney sections was used to confirm ShcA deletion in podocytes. Coomassie blue staining of protein gels was used to detect urinary albumin. Light and electron microscopy were used to assess glomerular morphology. Transcript levels of SHC1 in human renal disease were assessed using the Nephroseq database.
Results: Mice lacking podocyte ShcA were born at the expected Mendelian frequency and did not display overt renal impairment or changes in podocyte architecture beyond one year of age. In parallel, we correlated increased ShcA mRNA expression in the human kidney with proteinuria and reduced glomerular filtration rate.
Conclusion: Our studies reveal that ShcA is dispensable for normal kidney function, but its upregulation is associated with disease.
Keywords: Nephroseq; ShcA; glomerulus; knockout mice; podocyte.
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