title: A novel transgenic mouse model carrying human Tribbles related protein 3 (TRB3) gene and its site specific phenotype.
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.
authors.affiliation: Department of Drug Metabolism and Disposition, Graduate School of Pharmaceutical Sciences, Nagoya City University.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Sakai
authors.forename: Katsumi
authors.initials: K
authors.lastname: Fukamachi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Futakuchi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Miyoshi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuda
authors.forename: Masumi
authors.initials: M
authors.lastname: Suzui
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hayashi
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000235:genetics*; D053145:Cell Nucleus Size / Q000235:genetics / Q000502:physiology; D002522:Chlorocebus aethiops; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D022781:Hepatocytes / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D019426:Integrases / Q000235:genetics; D007668:Kidney / Q000378:metabolism / Q000648:ultrastructure; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D013154:Spleen / Q000378:metabolism / Q000648:ultrastructure; D014162:Transfection; D019076:Transgenes
chemical_list: D018797:Cell Cycle Proteins; D012097:Repressor Proteins; C474831:TRIB3 protein, human; D017346:Protein Serine-Threonine Kinases; C045073:Cre recombinase; D019426:Integrases