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.

New Fluorescent Indicator Alleles in Mice that Expand the Power of Recombinase-based Labeling to Uncover Cellular Diversity

This technology includes a series of recombinase responsive indicator alleles in genetically modified laboratory mice which uniquely permit non-invasive labeling of cells defined by the overlap of up to three distinct gene expression domains. In response to any combination of Cre, Flp and Dre recombinases, these alleles express high levels of eGFP and/or tdTomato that allow the visualization of cells in live and fixed tissue, including samples processed using modern tissue clearing techniques.

SARS-CoV-2 Neutralizing Nanobodies for Therapeutic and Diagnostic Uses

This technology involves the utilization of highly effective nanobodies, specifically camelid antibodies, derived from immunized llamas to neutralize SARS-CoV-2. Additionally, it employs a unique mouse model, called a "nanomouse," that is engineered to express antibody genes from camels, alpacas, and dromedaries. These nanobodies offer significant advantages over traditional human and mouse antibodies due to their smaller size, which allows them to effectively target and bind to specific areas on antigens.

DLX3-floxed mice (DLX3f/f) for Use in Drug Development and In Vivo Research Studies for Ectodermal Dysplasia Disorders

This technology includes the creation of DLX3-floxed mice, specifically designed for conditional deletion of the DLX3 gene via Cre-mediated recombination. This innovative approach aims to develop mouse models for studying ectodermal dysplasia disorders. Ectodermal dysplasias are a diverse group of genetic conditions affecting the development of ectodermal structures, including hair, teeth, and bones. The DLX3f/f mice are particularly valuable for modeling specific disorders such as Tricho-dento-osseous syndrome (TDO), Amelogenesis Imperfecta (AI), and Dentinogenesis Imperfecta (DI).

Mouse Models of Cryopyrin-Associated Periodic Syndrome (CAPS) for Drug Discovery

This technology includes mouse models that express versions of mouse cryopyrin protein containing mutations associated with human CAPS disease. We engineered mutations associated with three specific CAPS phenotypes (familial cold autoinflammatory syndrome (FCAS); Muckle-Wells syndrome (MWS); and neonatal onset multisystem inflammatory disease (NOMID)) into the mouse cryopyrin gene (called Nlrp3) to examine the roles of IL-1 β and related cytokines, and better characterize inflammasome functions.