Expression of stabilized beta-catenin in differentiated neurons of transgenic mice does not result in tumor formation.
BACKGROUND
Medulloblastomas, embryonal tumors arising in the cerebellum, commonly contain mutations that activate Wnt signaling. To determine whether increased Wnt signaling in the adult CNS is sufficient to induce tumor formation, we created transgenic mice expressing either wild-type or activated beta-catenin in the brain.


METHODS
Wild-type and mutant human beta-catenin transgenes were expressed under the control of a murine PrP promoter fragment that drives high level postnatal expression in the CNS. Mutant beta-catenin was stabilized by a serine to phenylalanine alteration in codon 37.


RESULTS
Expression of the mutant transgene resulted in an approximately two-fold increase in beta-catenin protein levels in the cortex and cerebellum of adult animals. Immunohistochemical analysis revealed nuclear beta-catenin in hippocampal, cortical and cerebellar neurons of transgenic animals but not in non-transgenic controls. Tail kinking was observed in some transgenic animals, but no CNS malformations or tumors were detected.


CONCLUSIONS
No tumors or morphologic alterations were detected in the brains of transgenic mice expressing stabilized beta-catenin, suggesting that postnatal Wnt signaling in differentiated neurons may not be sufficient to induce CNS tumorigenesis.
Kratz
John E
JE
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ceberha@jhmi.edu
Stearns
Duncan
D
Huso
David L
DL
Slunt
Hilda H
HH
Price
Donald L
DL
Borchelt
David R
DR
Eberhart
Charles G
CG
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin