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.

Vesicular Stomatitis virus (VSV)-based Vaccine against Sudan Virus

There are five known Ebolavirus species: Ebola virus (Zaire ebolavirus); Sudan virus (Sudan ebolavirus or SUDV); Taï Forest virus (Taï Forest ebolavirus, formerly Cote d'Ivoire ebolavirus); Bundibugyo virus (Bundibugyo ebolavirus); and Reston virus (Reston ebolavirus). Last year an ebolavirus outbreak resulted in 164 cases and 55 deaths. While there is an FDA-approved Ebola virus vaccine authorized for use against Ebola virus infections, ERVEBO, this vaccine is not effective against SUDV due to the significant variation between Ebola virus and SUDV.

Alpha-galactosidase-A Knockout Mouse Model for Studying Fabry Disease

This technology includes an alpha-galactosidase-A knockout mouse model that can be used to study Fabry disease, an X-linked lysosomal storage disorder. Alpha-galactosidase-A is a crucial enzyme responsible for the breakdown of glycolipids, particularly globotriaosylceramide (Gb3), within lysosomes. In Fabry disease, a rare and inherited lysosomal storage disorder, mutations in the GLA gene lead to deficient or non-functional alpha-galactosidase-A enzyme activity.

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.

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