RRC ID 31844
Author Sakai Y, Fukamachi K, Futakuchi M, Miyoshi I, Tsuda H, Suzui M, Hayashi H.
Title A novel transgenic mouse model carrying human Tribbles related protein 3 (TRB3) gene and its site specific phenotype.
Journal Biol Pharm Bull
Abstract Tribbles related protein 3 (TRB3) pseudokinase plays a crucial role in cell proliferation, migration and morphogenesis during development. In our recent study, an introduction of human TRB3 gene into mouse mammary tumor cells caused an increase of proliferation of tumor cells and their nuclear size. In the current study, to examine whether this gene causes de novo morphological changes in a specific organ site we have developed a novel variation of the transgenic mouse model that conditionally expresses human TRB3 (hTRB3) gene using Cre-recombinase (Cre)/loxP recombination system. By injecting hTRB3 transgene construct into pronuclei of mouse embryo, we eventually obtained four hTRB3 mice. The gene expression was controlled by infection of adenovirus-expressing Cre via the tail vein of hTRB3 mouse. In Cre-mediated hTRB3 mouse, expression of the hTRB3 protein was detected in the cytoplasm of hepatocytes in the liver. Expression of this protein was also seen in lymphocytes in the spleen, glomerular endothelial cells, and epithelial cells of collecting duct of the kidney. In hepatocytes of the hTRB3 mouse, nuclear size was significantly greater than that of the wild type mouse, indicating that hTRB3 can play a role at least in part in hepatic morphogenesis. The present animal model may provide a system for evaluation of de novo morphological changes induced by a specific transgene in a specific organ site.
Volume 37(6)
Pages 1068-74
Published 2014-1-1
DOI 10.1248/bpb.b14-00260
PII DN/JST.JSTAGE/bpb/b14-00260
PMID 24882419
MeSH Adenoviridae / genetics Animals COS Cells Cell Cycle Proteins / genetics* Cell Nucleus Size / genetics Cell Nucleus Size / physiology Chlorocebus aethiops Gene Expression* Gene Transfer Techniques* Genetic Vectors Hepatocytes / metabolism Hepatocytes / ultrastructure Humans Immunohistochemistry Integrases / genetics Kidney / metabolism Kidney / ultrastructure Liver / metabolism Liver / ultrastructure Mice, Inbred C57BL Mice, Transgenic / genetics* Phenotype Protein Serine-Threonine Kinases / antagonists & inhibitors* Protein Serine-Threonine Kinases / genetics Repressor Proteins / genetics* Spleen / metabolism Spleen / ultrastructure Transfection Transgenes*
IF 1.863
Times Cited 3
DNA material pCALNL5 (RDB01862) pxCANCre (RDB01675).