Tissue expression of nephrin in human and pig.
Nephrin is a major component of the glomerular filtration barrier. Mutations in the nephrin gene (NPHS1) are responsible for congenital nephrotic syndrome of the Finnish type (NPHS1). Nephrin was at first thought to be podocyte specific, but recent studies have suggested that nephrin is also expressed in nonrenal tissues such as pancreas and CNS. We studied the expression of nephrin in human and porcine tissues at different stages of development and correlated these findings to clinical characteristics of NPHS1 children. Immunofluorescence staining and Western blotting were used to detect nephrin protein in frozen tissue samples. Polyclonal antibodies against the intracellular part of nephrin were used in these analyses. In situ hybridization was used to detect nephrin mRNA in specimens from normal human subjects and patients with NPHS1. Nephrin protein was not detected in nonrenal tissues obtained from human and porcine fetuses, newborns, and infants. Likewise, nephrin mRNA expression was not observed outside kidney glomerulus in normal or NPHS1 children. The phenotype analysis of NPHS1 children with severe nephrin gene mutations supported the findings in the tissue expression studies and revealed no impairment of the neurologic, testicular, or pancreatic function in a great majority of the patients. The studies suggest that nephrin has no major clinical significance outside the kidney.
Kuusniemi
Arvi-Matti
AM
Hospital for Children and Adolescents and Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland.
Kestilä
Marjo
M
Patrakka
Jaakko
J
Lahdenkari
Anne-Tiina
AT
Ruotsalainen
Vesa
V
Holmberg
Christer
C
Karikoski
Riitta
R
Salonen
Riitta
R
Tryggvason
Karl
K
Jalanko
Hannu
H
D000818:Animals; D015153:Blotting, Western; D004314:Down Syndrome / Q000235:genetics; D005260:Female; D005919:Glomerular Filtration Rate; D005947:Glucose / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009154:Mutation; D009404:Nephrotic Syndrome / Q000151:congenital / Q000235:genetics; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism; D013045:Species Specificity; D013552:Swine; D013737:Testis / Q000473:pathology; D013997:Time Factors; D014018:Tissue Distribution
D008565:Membrane Proteins; D011506:Proteins; C113267:nephrin; D005947:Glucose