From mice to humans.

Fiona Mcmurray,Lee Moir,Roger D Cox

doi:10.1007/s11892-012-0323-2

Fiona Mcmurray, Lee Moir + Show 1 more

Open Access

https://doi.org/10.1007/s11892-012-0323-2

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Abstract

The genomes of many species have now been completely sequenced including human and mouse. Great progress has been made in understanding the complex genetics that underlie diabetes and obesity in human populations. One of the current challenges is the functional identification and characterization of the genes within loci that are being mapped. There are many approaches to this problem and this review outlines the valuable role that the mouse can play. We outline the mouse resources that are available to the research community, including knockouts with conditional potential for every gene, and the efforts of the International Mouse Phenotyping Consortium to attach phenotype information to these genes. We also briefly consider the potential of TALEN technology to tailor-make new mouse models of specific mutations discovered in humans. Finally, we consider the recent progress in characterizing the GWAS genes FTO, TCF7L2, CDKAL1, and SLC30A8 in engineered mouse models.

Highlights

Type 2 diabetes clearly has a genetic component and disease susceptibility reflects an interaction between multiple genes, environmental challenges, and age
To illustrate the application of mouse genetics in going “from mice to humans” we will consider 4 genes from human diabetes Genome wide association studies (GWAS) examined in recent studies; FTO, TCF7L2, CDK5 regulatory subunit associated protein 1-like 1 (CDKAL1), and SLC30A8 (Fig. 1), all of which had
The mouse has proven to be a useful model system for the exploration of the genetics of diabetes and has a role to play in translating the results of GWAS, alongside other approaches

Summary

Introduction

Type 2 diabetes clearly has a genetic component and disease susceptibility reflects an interaction between multiple genes, environmental challenges, and age. Human Genome wide association studies (GWAS) have so far associated over 50 genes with type 2 diabetes (reviewed in [2]). These studies identify single nucleotide polymorphisms (SNPs) that are associated with specific diseases. Identification of the underlying causative gene is necessary and there are a variety of approaches that may achieve this aim, including the use of mouse models. Often these genes were not previously associated with a disease and in some cases may be of unknown function. We highlight recent progress in the utilization of mouse models for the study of human type 2 diabetes loci and which illustrate the potential of the mouse to human (and back again) approach

Mouse Models for Diabetes Genes

New Mouse Resources

Genes in Man and Mouse

Conclusions