Lack of Cilia Protein Triggers Rare Kidney Disease

A recent study showed that one type of nephronophthisis (NPHP), a rare kidney disease of infants, children, and young adults, is linked to the gene for inversin, a protein found in cilia of renal tubular cells in the kidney.

Investigators at the University of Michigan Medical School (Ann Arbor, USA; www.umich.edu) found nine distinct recessive mutations in the inversin gene in nine infants with early-onset NPHP from seven different families. No inversin mutations were found in 100 healthy control subjects. Inversin protein interacts with proteins expressed by nephrocystin, the gene responsible for NPHP type 1. Both proteins are expressed in cilia and interact with beta-tubulin.

Deletion of the inversin gene from embryonic zebra fish, caused the fish to develop severe kidney cysts and heart defects. Injecting the abnormal embryos with mouse inversin messenger RNA restored normal development. Embryonic knockout mice lacking the inversin gene developed with their internal organs on the wrong side of their bodies (90%) or with serious heart defects (10%).

"The new twist is that virtually all proteins known to, if defective, give rise to renal disease in mice and in humans are expressed in cilia,” said senior author Dr. Friedhelm Hildebrandt, professor in the department of pediatrics at the University of Michigan Medical School. "Cilia seem to be structures designed to sense something. They seem to respond to mechanical signals or chemical signals from other cells in ways that regulate cell proliferation and cell development. If these signals are absent or defective, it could cause early developmental problems or it could affect mechanisms that repair damaged kidney cells.”



Related Links:
University of Michigan