A perspective on inversin.

Over the past 5 years, there has been increasing evidence for the role of primary (9+0) cilia in renal physiology and in establishing the left-right axis. The cilia in the renal tract are immotile and thought to have a sensory function. Cilia at the murine embryonic node have a vortical movement that sets up a leftward flow. Inversin, the protein defective in the inv mouse and in patients with type-2 nephronophthisis, localizes to both renal and node primary cilia. However, we present evidence that it is also expressed before the node forms and that its subcellular localization in renal tubular cells is not confined to the cilia. Its role in both the pathway determining left-right axis and renal function remains to be elucidated.

Expression analyses and interaction with the anaphase promoting complex protein Apc2 suggest a role for inversin in primary cilia and involvement in the cell cycle.

Homozygous inv mice lack a functional inversin protein and exhibit situs inversus plus severe cystic changes in the kidney and pancreas. Although the inversin sequence has provided few clues to its function, we and others have previously identified calmodulin as a binding partner. We now provide evidence that inversin interacts with the anaphase promoting complex protein Apc2. As expected of an Apc2 target, inversin possesses D-boxes and site-directed mutagenesis of the well-conserved D-box residues abrogates inversin-Apc2 interaction. An inversin-specific antibody reveals a dynamic expression pattern throughout the cell cycle and strong expression in the primary cilia of renal epithelium. Our data support a role for inversin in primary cilia and involvement in the cell cycle. Mutations of the proteins polaris, cystin and polycystin-2 which are expressed in renal epithelium primary cilia, lead to renal cystic changes. Aberrant cell proliferation is also involved in cyst development. The data reported here suggest that inversin may provide a link between these two mechanisms.

Changes in body composition and bone density after discontinuation of growth hormone therapy in adolescence: an interim report.

Growth hormone deficiency (GHD) in adults and children is associated with decreased lean tissue mass (LTM), increased fat mass and reduced bone mineral density (BMD). The changes in BMD and body composition, 6 and 12 months after ceasing GH treatment, were assessed using dual-energy X-ray absorptiometry in eight patients with GHD (age range, 13.8-17.5 years). Seven age-matched normal subjects who had completed growth were assessed at 0 and 12 months. Total body BMD was low at baseline (p < 0.05) in patients with GHD compared with the predicted values based on sex-specific regression equations, with height, weight and age taken into account. Total body, lumbar spine and femoral neck BMD increased in the patients and controls at 12 months. LTM decreased significantly by a mean of 1.37 kg in the patients with GHD at 12 months whereas there was a non-significant increase in LTM in the control group. The percentage of body fat increased in all patients with GHD at 6 and 12 months, from 27.2 +/- 11% (mean +/- SD) at baseline to 32 +/- 9.9% at 12 months (p = 0.009). There was no significant increase in mean percentage body fat in the control group. The ratio of android (trunk):gynoid (legs) fat was calculated using default settings of dual-energy X-ray absorptiometry. The mean android:gynoid fat ratio increased, though non-significantly, in patients with GHD at 12 months, with 6 of 7 showing an increase; no change was observed in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)