Phenotype of a calbindin-D9k gene knockout is compensated for by the induction of other calcium transporter genes in a mouse model.
CaBP-9k may be involved in the active calcium absorption and embryo implantation. Although we generated CaBP-9k KO mice to explore its function, no distinct phenotypes were observed in these KO mice. It can be hypothesized that TRPV5 and 6 and plasma membrane calcium ATPase 1b may play a role in the regulation of calcium transport to compensate CaBP-9k deficiency in its KO model.


BACKGROUND
Active calcium transport in the duodenum and kidney is carried in three steps: calcium entry through epithelial Ca2+ channels (TRPV5 and TRPV6), buffering and/or transport by calbindin-D9k (CaBP-9k) and -D28k (CaBP-28k), and extrusion through the plasma membrane calcium ATPase 1b (PMCA1b) and sodium/calcium exchanger 1. Although the molecular mechanism of calcium absorption has been studied using knockouts (KOs) of the vitamin D receptor and CaBP-28k in animals, the process is not fully understood.


METHODS
We generated CaBP-9k KO mice and assessed the phenotypic characterization and the molecular regulation of active calcium transporting genes when the mice were fed different calcium diets during growth.


RESULTS
General phenotypes showed no distinct abnormalities. Thus, the active calcium transport of CaBP-9k-null mice proceeded normally in this study. Therefore, the compensatory molecular regulation of this mechanism was elucidated. Duodenal TRPV6 and CaBP-9k mRNA of wildtype (WT) mice increased gradually during preweaning. CaBP-9k is supposed to be an important factor in active calcium transport, but its role is probably compensated for by other calcium transporter genes (i.e., intestinal TRPV6 and PMCA1b) during preweaning and renal calcium transporters in adult mice.


CONCLUSIONS
Depletion of the CaBP-9k gene in a KO mouse model had little phenotypic effect, suggesting that its depletion may be compensated for by calcium transporter genes in the intestine of young mice and in the kidney of adult mice.
Lee
Geun-Shik
GS
Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Lee
Kun-Yeong
KY
Choi
Kyung-Chul
KC
Ryu
Young-Han
YH
Paik
Sang Gi
SG
Oh
Goo Taeg
GT
Jeung
Eui-Bae
EB
D000327:Adsorption; D000818:Animals; D064026:Calbindins; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000096:biosynthesis* / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis* / Q000235:genetics; D004386:Duodenum / Q000254:growth & development / Q000378:metabolism; D010064:Embryo Implantation / Q000502:physiology; D017136:Ion Transport / Q000502:physiology; D007668:Kidney / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D010641:Phenotype; D064030:S100 Calcium Binding Protein G / Q000235:genetics; D050916:TRPV Cation Channels / Q000096:biosynthesis* / Q000235:genetics
D064026:Calbindins; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D009419:Nerve Tissue Proteins; D064030:S100 Calcium Binding Protein G; C576507:S100g protein, mouse; D050916:TRPV Cation Channels; C492240:Trpv5 protein, mouse; C446923:Trpv6 protein, mouse; D000252:Calcium-Transporting ATPases; D002118:Calcium