Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning.

1 alpha,25-Dihydroxyvitamin D3[1 alpha,25(OH)2D3], an active form of vitamin D, has roles in many biological phenomena such as calcium homeostasis and bone formation, which are thought to be mediated by the 1 alpha,25(OH)2D3 receptor (VDR), a member of the nuclear hormone receptor superfamily. However, the molecular basis for the actions of 1 alpha,25(OH)2D3 in bone formation, its role during development and VDR genetic polymorphisms for predicting bone mineral density are uncertain. To investigate the functional role of VDR, we generated mice deficient in VDR by gene targeting. We report here that in VDR null mutant mice, no defects in development and growth were observed before weaning, irrespective of reduced expression of vitamin D target genes. After weaning, however, mutants failed to thrive, with appearance of alopoecia, hypocalcaemia and infertility, and bone formation was severely impaired as a typical feature of vitamin D-dependent rickets type II (refs 8, 9). Unlike humans with this disease, most of the null mutant mice died within 15 weeks after birth, and uterine hypoplasia with impaired folliculogenesis was found in female reproductive organs. These defects, such as alopoecia and uterine hypoplasia, were not observed in vitamin D-deficient animals. The findings establish a critical role for VDR in growth, bone formation and female reproduction in the post-weaning stage.

[Experimental and clinical studies on the intestinal anastomosis and reconstruction of the alimentary tract].

Healing process of anastomosis and its procedure were studied in following points: Four-interrupted sutures anastomosis in the Wistar rats revealed recanalization without leakage in 64 out of 69. Lymphangial recanalization through the anastomosis was completed within 21 days after operation by Gambee' layer-to-layer anastomosis. While 8 weeks were required by everted or inverted anastomosis. Serosal surface of invaginated intestinal segment of which length corresponded to x1-x2 luminal diameter in the telescoping anastomosis was covered within 8 weeks by the proliferated mucosae of the both proximal and distal segments. Telescoping anastomosis was found to be useful to make an intestinal valve which worked just the same as ileocoecal junction. IVH and elementary diet were effective on the healing of anastomosis. According to the above mentioned findings, following operative procedures were recommended: Esophago-jejunal conduit duodenostomy following total gastrectomy. Choledocho-jejunal conduit duodenostomy with the intestinal valve as bile duct reconstruction. Construction of the intestinal valve and an artificial sphincter using rectus abdominis muscle fibers for ileostomy or short bowel syndrome. Endorectal pull-through operation for anterior-resection of the rectum as well as for radical treatment of Hirschsprung' disease.