Compensatory induction of the TRPV6 channel in a calbindin-D9k knockout mouse: Its regulation by 1,25-hydroxyvitamin D3.
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 verified using gene knockout (KO) models. We previously generated calbindin-D9k (CaBP-9k) KO mice and reported that induction of expression of some calcium transport proteins can compensate for the CaBP-9k gene deficiency. In the current study, we have further clarified the compensatory regulation of calcium transport genes by two calcium regulating hormones, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and parathyroid hormone (PTH), in CaBP-9k KO mice, because the levels of these hormones differ between the KO and wild-type (WT) mice. The induction of transient receptor potential cation channel, subfamily V, member 6 (TRPV6) in the duodenum was observed in adult KO male mice but induction was not modified by physiologic doses of 1,25(OH)(2)D(3). Duodenal TRPV6 transcription in WT and female KO mice were modulated by 1,25(OH)(2)D(3) in a dose-dependent manner. This compensatory gene induction was not detected in the mice fed a vitamin D(3)-deficient diet. Compensatory gene induction was not affected by PTH. Thus, the compensatory expression of duodenal TRPV6 in the KO male mice may be tightly correlated with serum 1,25(OH)(2)D(3). Vitamin D receptor (VDR) transcription and protein levels were measured to examine whether VDR expression mediates differential regulation of duodenal TRPV6 between WT and KO mice, but expression and levels of VDR were similar in both genotypes. The compensatory TRPV6 transcripts in KO mice may be modulated by endogenous vitamin D(3) via other factors of VDR signaling complexes.
Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
Geun-Shik
GS
Lee
Eui-Man
EM
Jung
Kyung-Chul
KC
Choi
Goo Taeg
GT
Oh
Eui-Bae
EB
Jeung
D000818:Animals; D064026:Calbindins; D002117:Calcitriol / Q000378:metabolism* / Q000494:pharmacology; D004386:Duodenum / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D010281:Parathyroid Hormone / Q000494:pharmacology; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014808:Vitamin D Deficiency / Q000378:metabolism
D064026:Calbindins; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D064030:S100 Calcium Binding Protein G; C576507:S100g protein, mouse; D050916:TRPV Cation Channels; C120776:TRPV6 channel; D002117:Calcitriol