Generation of Smad3-null Mice and Smad4-conditional Mice

SMADs are a novel set of mammalian proteins that act downstream of TGF-beta family ligands. These proteins can be categorized into three distinct functional sets, receptor-activated SMADs (SMADs 1,2,3,5, and 8), the common mediator SMAD (SMAD 4), and inhibitory SMADs (SMADs 6 and 7). SMAD proteins are thought to play a role in vertebrate development and tumorigenesis.

A Mouse with a Targeted Mutation in the Uncoupling Protein-3 (upc3) Gene

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.

A Nurr1-Knockout Mouse Model for Parkinson's Disease and Stem Cell Differentiation

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.

A Mouse Model for Type 2 Diabetes

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.

Immortalized Rhesus macaque Bcl-6/Bcl-xL Stable B Cell Lines as Tools for HIV Antibody Discovery

Scientists at NIAID have developed two immortalized stable B cell lines from rhesus macaques that can have value as research tools for the discovery of neutralizing antibodies of simian origin against HIV and that may have value in the development of an HIV vaccine. These B cell lines encode human Bcl-6 and Bcl-xL proteins, which are major regulators of apoptosis. These B cell lines are derived from the lymph node of a rhesus macaque (RM) that was infected with SHIV.CH505.

Method to Detect and Quantify In Vivo Mitophagy

This technology includes a transgenic reporter mouse that expresses a fluorescent protein called mt-Keima, to be used to detect and quantify in vivo mitophagy. This fluorescent protein was originally described by a group in Japan and shown to be able to measure both the general process of autophagy and mitophagy. We extended these results by creating a living animal so that we could get a measurement for in vivo mitophagy. Our results demonstrate that our mt-Keima mouse allows for a straightforward and practical way to quantify mitophagy in vivo.

Transgene Free Non-human Primate Induced Pluripotent Stem Cells (iPSCs) for Use in Pre-clinical Regenerative Medicine Research

This technology includes rhesus macaque induced pluripotent stem cells (iPSCs) lines from multiple animals and various types of cells to establish this pre-clinical model. iPSCs are a type of pluripotent stem cell that can be generated from adult somatic cells. The iPSC technology holds great potential for regenerative medicine. Before clinical application, it is critical to evaluate safety and efficacy in a clinically-relevant animal model. We propose that non-human primate models are particularly relevant to test iPSC-based cell therapies.

Transgenic Mouse Expressing Cre for the Development for Delivery of Gene Therapy

This technology includes a mouse model containing a hypothetical, previously undescribed, gene that we have proven is expressed in hair cells of the inner ear and few other tissues in the body. The hair-cell limited expression of Cre is a genetic tool for creating conditional mutations affecting hair cells almost exclusively. Hair cells are the sensory receptors of both the auditory system and the vestibular system in the ears of all vertebrates.

Inhibition of Epoxide Hydrolase 1 in the Treatment of Cardiovascular Diseases

This technology includes EPHX1/EPHX2 null mice and showed that disruption of both EPHX1 and EPHX2 almost completely abolished hydrolysis of several EETs which can be used in the treatment of cardiovascular diseases. EPHX 1 is significantly involved in EET hydrolysis, and we believe the combined use of EPHX1 and EPHX2 inhibitors would provide a better alternative to currently available therapeutic options or the EPHX2-based therapies currently in trials for the treatment of cardiovascular diseases.

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