Research on Mice Identifies New Diabetes Genes

Scientists have discovered hundreds of genes involved in the development of diabetes and other metabolic diseases.

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Diabetes is among the top 10 causes of death worldwide. It’s responsible for 1.6 million deaths each year according to the World Health Organization. Diabetes could cause serious damage to the heart, blood vessels, eyes, kidneys and nerves over time.

The development of diabetes and other metabolic diseases is a complex process where lifestyle, environmental and genetic factors play a crucial role. Yet, many genes that cause diabetes are still unknown. An international team of researchers supported by the EU-funded INFRAFRONTIER2020 project has now identified hundreds of genes that could be key in the development of such diseases. The findings were published in the ‘Nature Communications’ journal.

Through its mouse phenotyping study, the researchers found novel links to metabolic traits for 429 genes in mice. In 51 of them, the link with disease had been completely unknown to scientists. They showed that 23 of these genes may play a role in human diabetes.

In order to identify ‘candidate genes’ for diabetes, the researchers examined knockout mice – each lacking a specific gene for metabolic dysfunction. Then, they compared their results with genome data collected from human patients to establish whether the missing gene is involved in important metabolic processes and can be linked to human diseases.

In a press release, Martin M. Hrabě de Angelis, head of the Institute of Experimental Genetics at the Munich Helmholtz Centre, a member research centre of the International Mouse Phenotyping Consortium (IMPC), said: “Our analysis of the phenotyping data has identified a total of 974 genes whose loss has strong effects on glucose and lipid metabolism.” Prof. Hrabě de Angelis, who led the study, added “for more than a third of the genes, no connection to metabolism was known previously.”

The IMPC initiative systematically determines the function of every gene in the mouse genome. It creates computational models of disease in the mouse to explore how diseases arise and develop in humans.

The study concluded: “By linking gene functions to metabolic disorders, our protocol and the identification of metabolic relevant genetic elements will accelerate the understanding of human disease.”

The INFRAFRONTIER Research Infrastructure (RI) integrates European Mouse Clinics and the European Mouse Mutant Archive to ensure access to mouse models for basic research of human health and disease, and to translate this knowledge into therapeutic approaches. The expanded INFRAFRONTIER2020 network, coordinated by the INFRAFRONTIER GmbH, is expected to enhance the sustainable operation of INFRAFRONTIER RI.

The ongoing INFRAFRONTIER2020 (Towards enduring mouse resources and services advancing research into human health and disease) project also aims to address major societal challenges in human health by customised service pilots supporting research into common and rare diseases.

Studying the biology of mice is useful for understanding disease in humans who share 98 % of their genes with these rodents. By deciphering cause and effect – the causal genetic links – researchers are trying to understand how diseases arise, develop therapeutic interventions or even prevent an outbreak.

Source : CORDIS