Research article

Expression of stabilized β-catenin in differentiated neurons of transgenic mice does not result in tumor formation

John E Kratz¹ , Duncan Stearns¹ , David L Huso² , Hilda H Slunt¹ , Donald L Price¹ , David R Borchelt¹ and Charles G Eberhart¹

¹Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

²Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

author email corresponding author email

BMC Cancer 2002, 2:33doi:10.1186/1471-2407-2-33

Published:	2 December 2002

Abstract

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 β-catenin in the brain.

Methods

Wild-type and mutant human β-catenin transgenes were expressed under the control of a murine PrP promoter fragment that drives high level postnatal expression in the CNS. Mutant β-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 β-catenin protein levels in the cortex and cerebellum of adult animals. Immunohistochemical analysis revealed nuclear β-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 β-catenin, suggesting that postnatal Wnt signaling in differentiated neurons may not be sufficient to induce CNS tumorigenesis.