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Pathophysiology of Calcium Processing Genes in Knockout Animal Models

  • 언어ENG
  • URLhttps://db.koreascholar.com/Article/Detail/191541
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발생공학 국제심포지엄 및 학술대회 (International Symposium on Developmental Biotechnology)
한국동물번식학회 (The Korean Society of Animal Reproduction)
초록

Active calcium transport is carried out by calcium channel proteins, cytosolic buffering or transfer proteins, and pump proteins. Several components of this transport system have recently been determined using gene knockout (KO) models. The calbindin‐ D9k/28k and calbindin‐D9k/TRPV6 double KO mice were generated and reported that induction of expression of some duodenal calcium transport proteins can compensate for the CaBP‐9k gene deficiency. In CaBP‐9k KO mice, the levels of these hormones differ between the KO and wild‐type (WT) mice. The induction of TRPV6 in the duodenum was observed in adult KO male mice but induction was not modified by physiologic doses of 1,25(OH)2D3 and compensatory gene induction was not affected by PTH. Duodenal TRPV6 transcription in WT and female KO mice were modulated by 1,25(OH)2D3 in a dose‐dependent manner. Under calcium‐deficient dietary conditions, in DKO mice, serum calcium levels and bone length were decreased. The intestinal and renal expression of TRPV6 mRNA was significantly decreased in DKO mice fed a calcium‐deficient diet as compared to CaBP‐28k KO or WT mice, and DKO mice died after 4 weeks on a calcium‐deficient diet. Body weight, bone mineral density (BMD) and bone length were significantly reduced in all mice fed a calcium and 1,25‐(OH) D3‐ eficient diet, as compared to a normal diet, and none of the mice survived more than 4 weeks. Using microarray analysis, NCKX3 was identified as a gene that was differentially expressed in the kidneys of female and male mice. Although any hormones did not alter NCKX3 expression, however, aldosterone and hydrocortisone did down‐regulate renal NCKX3 expression in female mice. Taken together, these results indicate that deletions of CaBP‐9k and 28k has a significant effect on calcium processing under calcium‐deficient conditions, confirming the importance of dietary calcium and 1,25‐(OH)2D3 during growth and development

저자
  • Eui-Bae Jeung(Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University)