Cataract is the most common cause of blindness worldwide, with an estimated 25 million blind and 119 million visually impaired individuals worldwide. Over 20 million adults in the US alone are currently diagnosed with cataracts making this disease a major health concern. The incidence of cataract increases with age and a number of etiologic factors have been proposed in the pathogenesis of age-related cataract in humans including genetic factors, environmental factors and metabolic and biochemical changes in the crystalline lens.

Diabetes affects over 120 million people worldwide (16 million in the US) and is a major health problem with associated health costs estimated at almost $100 billion dollars. Type 2 diabetes affects as many as 10% of the population of the Western World (with 15 million patients in the US alone) and arises from a heterogeneous etiology, with secondary effects from environmental influences. Risk factors for type 2 diabetes include obesity, high blood pressure, high triglycerides and age.

Osteoarthritis (OA) is the most common form of arthritis and affects more than 20 million Americans, costing billions of dollars in health care annually. Osteoarthritis is caused by the breakdown of joint cartilage, leading to a loss of the cartilage "cushion" between the bones of the joints. Risk factors associated with OA include age, obesity, traumatic injury and overuse due to sports or occupational stresses. There is no cure for OA and current treatments are directed at the symptomatic relief of pain, and at improving and maintaining joint function.

This invention concerns "knockout" animals, including mice, which have a deficit of functional steroid hormone receptors, DNA constructs containing the mutations, and methods for producing the animals. The mutation is introduced into the animal or its ancestors at an embryonic stage. These knockout animals provide a model system for studying the biological role of hormones, including steroid hormones and sex steroids, in growth, development, morphological differentiation, and sexual and reproductive behavior and cycles, etc.

Embryonic stem cells (ESCs) are pluripotent cells that can be cultured indefinitely, and maintain their capability to differentiate into all cell lineages. To maintain these cells as well as various types of related induced stem cells and progenitor cells in culture, Mouse Embryonic Fibroblasts (MEFs) are routinely used as feeder cells, largely to serve as a source of Leukemia Inhibitory Factor (LIF). ESCs can also be cultured without feeders if the medium is supplemented with recombinant LIF and other factors.

SMAD7 conditional knockout mice are available for licensing. SMAD7 can be knocked out by breeding with CRE-recombinase transgenic mice with a variety of promoters to yield tissue or cell type-specific deletions of SMAD7. SMAD7 has been shown to play a role in bone morphogenesis, cardiovascular tissue generation, immune regulation and fibrosis. Therefore, these mice provide a unique model to examine the role of the SMAD7 gene in disease processes that involve immunological, fibrotic, or cardiovascular components.

This is a mouse model available to study T-cell differentiation. Growth factor independent 1 (GFi-1) is a transcriptional repressor that is transiently induced during T-cell activation. This knockout mouse line is a GFi-1[flox/flox] introduced into a mouse Cre controlled by a CD4 promoter, which allows selective removal of GFi-1 exclusively in T-cells. It has thus-far been used to demonstrate that GFi-1 plays a critical role in enhancing Th2 cell expansion and repressing induction of Th17 and CD103+ iTreg cells.

This technology relates to novel animal models of several human bone diseases that have been linked to enhanced BMP signaling. More specifically, this mouse model expresses a mutant receptor for BMP, known as Alk2 that is always actively signaling. This receptor is under the control of the Cre-loxP system, which allows control of expression of the mutant Alk2 in both a developmental and tissue-specific manner. As a result, the enhanced signaling conditions exhibited in multiple human bone-related diseases can be studied with the same animals.

The researchers have generated Nurr1-knockout mice via genomic locus inactivation using homologous recombination.

Transcription factor Nurr1 is an obligatory factor for neurotransmitter dopamine biosynthesis in ventral midbrain. From a neurological and clinical perspective, it suggests an entirely new mechanism for dopamine depletion in a region where dopamine is known to be involved in Parkinson's disease. Activation of Nurr1 may be therapeutically useful for Parkinson's disease patients; therefore, the mice would be useful in Parkinson's disease research.

The NIH announces the development of a transgenic mouse with a targeted mutation in the ucp3 gene. The ucp3 gene is implicated I the function of regulating energy metabolism. This regulatory function is thought to be accomplished by changing metabolic efficiency (causing energy expended as heat rather than used for ADP/ATP conversion) and/or by participating in fat metabolism. The mutation should inactivate the ucp3 function and the mouse provided a testing vehicle for the above hypotheses.