International Mammalian Genome Society


The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

G22 The Megencephaly Mouse has Disturbances in the Cholecystokinin (CCK), Enkephalin ENK), Galanin (GAL) and Neuropeptide Y (NPY) Systems

Susanna Peterssona, Catharina Lavebratta, Martin Schallinga and Tomas Hökfeltb. Depts. of Molecular Medicinea and Neuroscienceb, Karolinska Institutet, Stockholm, Sweden

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 neurological and motor disturbances with recurring seizure-like activity. Previous studies suggest that the brain enlargement results from hypertrophy of brain cells, rather than hyperplasia. No structural abnormalities or edema have been found. We have previously reported that the mceph / mceph mice suffer from major disturbances in the insulin-like growth factor (IGF) system in the hippocampal formation, amygdala and parietal cortex. In this study we found disturbances in the neuropeptide systems of cholecystokinin (CCK), enkephalin (ENK), galanin (GAL) and neuropeptide Y (NPY) in brains from mceph / mceph compared to wildtype mouse brains as studied by immunohistochemistry and in situ hybridization. For CCK, mceph / mceph brains had region-specific up- and down-regulations of peptide-like immunoreactivity (LI) and mRNA levels in several hippocampal layers and increased levels in parietal cortex. ENK-LI was significantly elevated in CA3 of the hippocampus and the ventral cortices, whereas mRNA expression was up-regulated in piriform / entorhinal cortex, dentate gyrus granule cells and down-regulated in CA1 of the mceph / mceph brains. The normal GAL-immunoreactive (IR) nerve terminal plexus of telencephalon was diminished in the mceph / mceph brains, but these brains displayed increased levels of both GAL-LI and mRNA in several hippocampal layers and interneurons, and also in the ventral cortices. NPY-LI and mRNA was increased mainly in hippocampal layers, parietal cortex, amygdala and piriform / entorhinal cortex. CCK, ENK, GAL and NPY are peptides with so far not fully defined physiologic functions in the mammalian nervous system. They seem, however, to be involved in regulation of growth and development, trauma responses and seizure sensibility. Whether or not these distinct changes in peptide-immunoreactivities and mRNA levels in discrete brain regions shown here are associated with the excessive growth of the megencephaly mouse brain remains to be elucidated.

 


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