The megencephaly mouse has disturbances in the insulin-like growth factor (IGF) system

Megencephaly. enlarged brain, is a major sign in several human neurological diseases. The mouse model for megencephaly, mceph / mceph, has an enlarged brain and a lowered body weight. In addition, it displays several neurolog ical and motoric disturbances. previous studies suggest that the brain enla rgement results from hypertrophy of the brain cells, rather than hyperplasi a No structural abnormalities, edema or increased myelination have been fou nd. In this study, a major imbalance in the mRNA expression of molecules in the insulin-like growth factor (IGF) system was found in brains of 9-10 we eks old mceph /mceph mice compared to + / + wild-type mice. In mceph/mceph brains, we found upregulation of IGF binding proteins (BP)-2, -1, -5, and - 6 mRNA, the regulating hormone transforming growth factor (TGF)beta 1 mRNA and also a local downregulation of IGFBP-5 mRNA compared to wild-type brain s by in situ hybridization. The altered expression of these mRNA species is colocalized in cerebral cortex, hippocampus, amygdala and piriform/entorhi nal cortex. The mceph /mceph mice express less of the myelin component prot eolipid protein (PLP) mRNA in corpus callosum. No expression difference of the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in b rain or IGF system components in liver was found between mceph /mceph and w ild-type mice. These data suggest that the IGF system has an important role in the excessive growth of the mceph/mceph brains. (C) 1999 Elsevier Scien ce B.V. All rights reserved.