An integrated and translational research consortium to study dysfunction and degeneration of the nervous system. They aim to use data from the IMPC to further investigate mouse genes important for disease-related neuroscience research, including mitochondrial disease, neurodegeneration, neuromuscular diseases, neuropsychiatric disease and sensory systems. The consortium consists of both basic scientists and clinicians, as well as input from human geneticists, with a particular focus on the translational impact of their research on human neurological disorders.
MacII: Macrophage Biology and Innate Immunity
The Macrophage Biology and Innate Immunity consortium have set up an in vitro screening panel to investigate the effect of a large number of gene knockouts on innate immunity. They examine the impact of the knockouts on myeloid differentiation, innate immunity and antigen presentation, and are working to identify the functions of genes expressed specifically in cells of the innate immune system and in other more general cell functions.
Models for Disorders of Bone and Cartilage
Uses IMPC data from MRC Harwell to establish and characterise mouse models for the major human bone and cartilage disorders, including osteoporosis, osteoarthritis, skeletal trauma, chondrocalcinosis, Paget’s disease and skeletal dysplasia. They aim to elucidate the underlying biological mechanisms in these disorders and provide in vivo models for pre-clinical studies, leading to novel approaches for the prevention and treatment of bone and cartilage disorders.
MADD: Mouse Models to Accelerate Drug Discovery
MADD is working with researchers in China to accelerate drug discovery through the use of mouse models from the IMPC, focusing on genes involved in the protein ubiquitylation system. They are carrying out a systematic screen of the genes of the deubiquitylases, E2 conjugating enzymes, F-Box substrate targeting subunits of cullin containing E3 ligases and HECT E3-ligases, with a view to identifying novel drug targets.
UK GoLD: UK Genetics of Liver Disease
The UK GoLD consortium is interested in genes and mechanisms involved in the pathogenesis of liver disease. They focus on: addiction behaviour, a key risk factor for going on to develop liver disease; mechanisms of metabolic liver disease, inflammation and hepatocellular injury; and identifying potential therapies that can prevent hepatic fibrosis progression or promote liver regeneration.
nPAD: Neurodegenerative Processes of Ageing and Disease
The nPAD consortium aims to use IMPC mouse models to define early events associated with neurodegenerative disease and ageing, with the intention of identifying intervention strategies to prevent disease progression in humans. Specifically, they are working to identify phenotypic biomarkers indicative of neurodegeneration, find key genes and proteins involved in triggering neurodegeneration, examine the contribution of neuronal, synaptic and glial dysfunction, investigate the impact of environmental factors and study the underlying molecular mechanisms.
Respiratory Development and Disease Research
By identifying and utilising mouse models obtained through the IMPC, the Respiratory Development and Disease Research consortium is conducting research into respiratory diseases. They are exploring aspects such as resilience to disease, the mechanism and impact of chronic lung inflammation, and the impact of ageing, as well as potential treatment options such as the use of regenerative medicine.
MODO: Models of Disease and Obesity
MODO is using our IMPC mice to investigate the molecular determinants of nutrient sensing and energy balance, covering aspects such as control of food intake, energy expenditure and weight gain. They aim to determine how alterations in these pathways can lead to obesity, Type 2 diabetes and associated metabolic complications, and use this information to identify and develop new treatments.
Genetics of Normal and Malignant Haematopoiesis
This consortium seeks to use secondary and tertiary phenotyping platforms to complement the IMPC pipeline and improve our understanding of the genes involved in haematopoiesis. In particular, they are identifying genes and pathways that control the development and homeostasis of the normal haematopoietic system, as well as genes that cause and modify malignant haematopoietic syndromes.
Kidney and Urogenital System
The Kidney and Urogenital System consortium uses IMPC mouse models to research renal and urogenital dysfunction. They are focusing on the glomerular, tubular, developmental, and cystic genes involved, although attention is also being paid to cross-boundary interactions to identify pleiotrophic effects. This has particular importance, as it is anticipated that individual genes will influence multiple renal phenotypic traits.
Cardiovascular Trait Consortium
This consortium investigates cardiovascular traits such as blood pressure, electrocardiographic measures, ventricular dysfunction and heart failure. They aim to characterise a series of new mouse models for candidate genes derived from human genome-wide association studies (GWAS) and functional experimentation. Their results may facilitate innovative drug development aimed at preventing these traits and so improve prognosis.
TeRiFiC: Tissue Remodelling and Fibrosis Research
Fibrotic diseases are a leading cause of morbidity and mortality and are relatively intractable to current treatments, and the response of any organ to tissue damage involves a carefully choreographed series of cellular interactions. This consortium aims to define the critical regulatory networks underlying the pathogenesis of organ/tissue-based fibrosis and tissue remodelling processes, as well as identify organ-selective and common anti-fibrotic targets.
Mouse Eyes and Vision Research
The Mouse Eyes and Vision Research consortium is generating mouse models of human vision and eye disease for investigation of disease mechanisms and therapies. They aim to identify the pathways that underlie normal eye function and understand how these are disrupted in disease, providing a platform for therapeutic developments.
This consortium identify, develop and analyse IMPC mouse models of congenital malformations (birth defects). They aim to use these to understand the development of birth defects affecting a range of organ and other body systems in the mammalian embryo and fetus, as well as establish tools that could be translated into clinical diagnosis, therapy and prevention.
Ion Channel Consortium
This consortium intends to use IMPC knockout mice from MRC Harwell to investigate ion channel genes and their role in associated phenotypes.