To determine the nature, extent, and severity of renal involvement in Laurence-Moon-Biedl syndrome (obesity, mental retardation, polydactyly, hypogonadism, and pigmented retinal dystrophy), we evaluated 20 of 30 patients with the disorder identified from ophthalmologic records in Newfoundland. The mean age was 31 years, and seven were male. All 20 patients had structural or functional abnormalities of the kidneys or both. Three had end-stage renal disease, with two requiring maintenance hemodialysis. The remaining 17 patients had normal serum creatinine values and estimated creatinine clearances. Half the subjects had hypertension. Fourteen of 17 patients could not concentrate urine above 750 mOsm per kilogram of body weight even after vasopressin, whereas all 10 normal controls could. Urinary pH decreased below 5.3 after ammonium chloride administration in all 15 normal controls, but in only 13 of 18 patients. Calyceal clubbing or blunting was evident in 18 of 19 patients studied by intravenous pyelography; 13 patients had calyceal cysts or diverticula. Seventeen of 19 patients had lobulated renal outlines of the fetal type. Four patients had diffuse renal cortical loss, but only two of these had renal insufficiency. We conclude that Laurence-Moon-Biedl syndrome includes the presence of renal abnormalities.

The purpose of the present study was to characterize in detail the 24 h blood pressure (BP) phenotype of mice lacking the gene for endothelial nitric oxide synthase (eNOS_/_) and the corresponding control strain (C57Bl/6J). Twenty-four hour BP recordings were made in conscious 12-to 16-week-old male mice 10 days following the implantation of a BP telemeter (n = 9 per group). The BP and heart rate of both strains were markedly affected by brief locomotor activity cycles, resulting in bimodal distributions of BP and heart rate within both light and dark periods. Data from active periods were associated with the higher of the two modes, whereas data from inactive periods were associated with the lower of the two modes. In eNOS_/_ mice, the 24 h average BP level was significantly elevated (+15 %, 104 ± 2 vs. 119 ± 1 mmHg), as was its daily range (+44 %), its coefficient of variation (+26 %), dark-light difference (+48 %), and the separation of the two modes of its distribution (+41 %). Pulse pressure was also significantly greater (+23 %) in eNOS_/_ mice. The 24 h heart rate level did not differ between control and eNOS_/_ mice. Considerable variation was noted among previously published values of BP in eNOS_/_ mice, but not in the corresponding control mice. Our results indicate that eNOS_/_ mice have mild hypertension that is accompanied by more pronounced increases in BP lability and/or reactivity. Our results also demonstrate a marked effect of locomotor activity on BP in mice, which may confound short-term measurements of BP.

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PTH and PTHrP both act in the regulation of fetal mineral metabolism. PTHrP regulates placental calcium transfer, fetal blood calcium, and differentiation of the cartilaginous growth plate into endochondral bone. PTH has been shown to influence fetal blood calcium, but its role in skeletal formation remains undefined. We compared skeletal morphology, mineralization characteristics, and gene expression in growth plates of fetal mice that lack parathyroids and PTH (Hoxa3 null) with the effects of loss of PTHrP (Pthrp null), loss of PTH/PTHrP receptor (Pthr1 null), and loss of both PTH and PTHrP (Hoxa3 null x Pthrp null). Loss of PTH alone does not affect morphology or gene expression in the skeletal growth plates, but skeletal mineralization and blood calcium are significantly reduced. In double-mutant fetuses (Hoxa3 null/Pthrp null), combined loss of PTH and PTHrP caused fetal growth restriction, limb shortening, greater reduction of fetal blood calcium, and reduced mineralization. These findings suggest that 1) PTH may play a more dominant role than PTHrP in regulating fetal blood calcium; 2) blood calcium and PTH levels are rate-limiting determinants of skeletal mineral accretion; and 3) lack of both PTH and PTHrP will cause fetal growth restriction.