Abstract

Owing to the overlapping and redundant roles of the seven mammalian nucleoside transporters (NTs), which belong to two protein families (ENTs and CNTs), the physiological importance of individual NTs has been difficult to assess. Mice that have NT genes knocked out can be a valuable tool in gaining an understanding of the NT proteins. We have generated a strain of mice that is homozygous for a disruption mutation between exons 2 and 3 of the mouse equilibrative nucleoside transporter, mENT1. We have undertaken a quantitative survey of NT gene expression in 10 tissues, as well as microarray analysis of heart and kidney, from wild-type and mENT1 knockout mice. Rather than a consistent change in expression of NT genes in all tissues of mENT1 knockout mice, a complex pattern of changes was found. Some genes, such as those encoding mCNT1 and mCNT3 in colon tissue, exhibited increased expression, whereas other genes, such as those encoding mCNT2 and mENT4 in lung tissue, exhibited decreased expression. Although mCNT3 has been shown to be important in human and rat kidney tissue, we were unable to detect mCNT3 transcripts in the kidney of either the wild-type or mENT1 knockout mice, suggesting differences in renal nucleoside resorption between species.

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