Podocyte-specific knockout of myosin 1e disrupts glomerular filtration.
Myosin 1e (myo1e) is an actin-dependent molecular motor that plays an important role in kidney functions. Complete knockout of myo1e in mice and Myo1E mutations in humans are associated with nephrotic syndrome and focal segmental glomerulosclerosis. In this paper, we tested the hypothesis that myo1e is necessary for normal functions of glomerular visceral epithelial cells (podocytes) using podocyte-targeted knockout of myo1e. Myo1e was selectively knocked out in podocytes using Cre-mediated recombination controlled by the podocin promoter. Myo1e loss from podocytes resulted in proteinuria, podocyte foot process effacement, and glomerular basement membrane disorganization. Our findings indicate that myo1e expression in podocytes is necessary for normal glomerular filtration and that podocyte defects are likely to represent the primary pathway leading to glomerular disease associated with Myo1E mutations.
Dept. of Cell and Developmental Biology, SUNY Upstate Medical Univ., 750 E. Adams St., Syracuse, NY 13210, USA.
Sharon E
SE
Chase
Christina V
CV
Encina
Lindsay R
LR
Stolzenburg
Arthur H
AH
Tatum
Lawrence B
LB
Holzman
Mira
M
Krendel
D000818:Animals; D004195:Disease Models, Animal; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D024461:Myosin Type I; D009218:Myosins / Q000235:genetics / Q000378:metabolism*; D050199:Podocytes / Q000378:metabolism*; D011507:Proteinuria / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
C505821:Myo1e protein, mouse; D024461:Myosin Type I; D009218:Myosins