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Functional analysis of the mouse G90 gene


Meunier,  Dominique
Max Planck Society;

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Meunier, D. (2003). Functional analysis of the mouse G90 gene. PhD Thesis, Albert-Ludwigs-Universität, Freiburg im Breisgau.

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The G90 gene was isolated a few years ago in a screen aimed at identifying genes expressed differentially between the small and large intestines of adult mice. This novel mouse gene shows no homology to known genes or gene families and its function is as yet unknown. However, G90 exhibits several interesting characteristics, including an intriguing mouse strain-dependent allelic usage and a distinct expression pattern in embryonic and adult mouse tissues, as well as in mouse intestinal tumours. It has previously been shown that G90 expression is restricted to post-mitotic cells in the intestine and testis of adult mice, thus suggesting a role in the control of proliferation and/or differentiation. In an attempt to get an insight into the possible function of G90, a detailed characterization of this gene was undertaken. First, RT-PCR and RNA FISH analyses revealed that G90 is monoallelically expressed in the majority of adult mouse intestinal cells; the mechanisms underlying the allelic expression of this gene remain however unknown. Then, database analyses led to the discovery that G90, which was first described as a noncoding RNA, in fact encodes a short protein conserved throughout mammalian and vertebrate evolution, a finding that strongly supports the view that this novel gene is functional. The detailed analysis of the spatiotemporal expression pattern of G90 during mouse embryonic development supported the hypothesis that this gene might be involved in the control of proliferation or differentiation: the gene was found to be expressed at high levels in specific structures of the developing head and a clear correlation between G90 expression and absence of proliferation could be observed in most of these tissues. However, the analysis of transgenic mice expressing the human G90 gene, as well as the use of various candidate gene and and microarray analysis approaches, failed to establish a link between G90 and a number of important regulators of the cell cycle, including the cyclin-dependent kinase inhibitors CDKN1A and CDKN1B, and the tumour suppressor TP53. Furthermore, the expression of the human G90 gene in embryos and mice did not cause any obvious phenotype, thus bringing no conclusive evidence as to the possible function of G90. However, the G90 gene was found to be specifically expressed in gastrointestinal tumours derived from Apc-deficient mice, as well as in several human colorectal cancers. Interestingly, its expression in such tumours appeared to correlate with defects in the Wnt signalling pathway. These findings suggest that G90 might play a role in the development or progression of gastrointestinal tumours. Thus, although the function of the G90 gene could not be elucidated in the course of the present study, the results obtained clearly indicate that this gene is likely to be functional. Additional studies should help to clarify the putative function of G90 in proliferation, differentiation, tumorigenesis and other cellular processes.