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Integrative analysis of pathology, mRNA and microRNA in a polygenic diabetes model, NONcNZO10/LtJ mice

ABSTRACT: The NONcNZO10/LtJ mouse is a polygenic model of type-2 diabetes (T2D) that shows moderate obesity and diabetes, and is regarded as a good model reflective of the conditions of human T2D. In this study, we analyzed pathological changes of pancreases with the progress of time by using histopathology and gene expression analysis, including microRNA. A number of gene expression changes associated with decreased insulin secretion (possibly regulated by miR-29a/b) were observed, and zinc homeostasis (Slc30a8, Mt1 and Mt2) or glucose metabolism (Slc2a2) was suggested as being the candidate mechanism of pancreas failure in NONcNZO10/LtJ mice. These results demonstrate NONcNZO10/LtJ mice have a complex pathogenic mechanism of diabetes, and moreover, this fundamental information of NONcNZO10/LtJ mice would offer the opportunity for research and development of a novel antidiabetic drug.

ORGANISM(S): synthetic construct Mus musculus

PROVIDER: GSE83241 | GEO | 2016/06/30

SECONDARY ACCESSION(S): PRJNA325351

REPOSITORIES: GEO

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Integrative analysis of pathology, mRNA and microRNA in a polygenic diabetes model, NONcNZO10/LtJ mice

Project description:The NONcNZO10/LtJ mouse is a polygenic model of type-2 diabetes (T2D) that shows moderate obesity and diabetes, and is regarded as a good model reflective of the conditions of human T2D. In this study, we analyzed pathological changes of pancreases with the progress of time by using histopathology and gene expression analysis, including microRNA. A number of gene expression changes associated with decreased insulin secretion (possibly regulated by miR-29a/b) were observed, and zinc homeostasis (Slc30a8, Mt1 and Mt2) or glucose metabolism (Slc2a2) was suggested as being the candidate mechanism of pancreas failure in NONcNZO10/LtJ mice. These results demonstrate NONcNZO10/LtJ mice have a complex pathogenic mechanism of diabetes, and moreover, this fundamental information of NONcNZO10/LtJ mice would offer the opportunity for research and development of a novel antidiabetic drug. To identify the diabetes related genes that changed expression during the development of T2D in NONcNZO10/LtJ mice, we analyzed gene expression profiles of 7-, 13-, and 22-week old NONcNZO10/LtJ mice using GeneChip Mouse Gene 2.0 ST Arrays. On the other hand, we compared gene expression profiles of 7-week old NONcNZO10/LtJ mice with 7-week old NON/ShiLtJ mice to investigate the differences of gene expression before developing T2D. Furthermore, to validate the hypothesis generated by the results of mRNA analysis, we identified differentially expressed microRNAs in 13- and 22-week compared with 7-week old NONcNZO10/LtJ mice using Affymetrix miRNA GeneChip 3.0 Arrays.

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