Abstract

Many neurodegenerative diseases have a hallmark regional and cellular pathology. Gene expression analysis of healthy tissues may provide clues to the differences that distinguish resistant and sensitive tissues and cell types. Comparative analysis of gene expression in healthy mouse and human brain provides a framework to explore the ability of mice to model diseases of the human brain. It may also aid in understanding brain evolution and the basis for higher order cognitive abilities. Here we compare gene expression profiles of human motor cortex, caudate nucleus, and cerebellum to one another and identify genes that are more highly expressed in one region relative to another. We separately perform identical analysis on corresponding brain regions from mice. Within each species, we find that the different brain regions have distinctly different expression profiles. Contrasting between the two species shows that regionally enriched genes in one species are generally regionally enriched genes in the other species. Thus, even when considering thousands of genes, the expression ratios in two regions from one species are significantly correlated with expression ratios in the other species. Finally, genes whose expression is higher in one area of the brain relative to the other areas, in other words genes with patterned expression, tend to have greater conservation of nucleotide sequence than more widely expressed genes. Together these observations suggest that region-specific genes have been conserved in the mammalian brain at both the sequence and gene expression levels. Given the general similarity between patterns of gene expression in healthy human and mouse brains, we believe it is reasonable to expect a high degree of concordance between microarray phenotypes of human neurodegenerative diseases and their mouse models. Finally, these data on very divergent species provide context for studies in more closely related species that address questions such as the origins of cognitive differences.

Highlights

  • We compare and contrast gene expression in three different regions of the human brain, motor cortex, caudate, and cerebellum, to identify genes that are differentially expressed between the regions

  • Animal models of human neurodegenerative and psychiatric disorders, mouse models, have assumed a central role in biomedical research aimed at discovering the causes of disease and generating novel, mechanism-based treatments

  • To what degree can a mouse brain serve as a model for a human brain? Here we begin to address this question by looking at patterns of gene expression across three corresponding regions of mouse and human brains

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Summary

Introduction

We compare and contrast gene expression in three different regions of the human brain, motor cortex, caudate, and cerebellum, to identify genes that are differentially expressed between the regions. We seek to identify genes that show patterned expression. Knowledge of such regionally enriched genes may provide insight into the development and biochemistry of different brain structures. This information may hold potential biomedical implications. Many neurodegenerative diseases, such as Huntington’s disease, have a hallmark regional and cellular pathology affecting one or another of these regions while sparing the others. It is reasonable to assume that unique susceptibilities in disease may relate to distinctive brain gene expression patterns in health

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