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.

A Mouse Cell Line Engineered to Produce Camelid Nanobodies for Diagnostic and Therapeutic Use

This technology includes the development of a mouse line capable of producing single-chain antibodies (nanobodies). Nanobodies, identified initially from Camelidae (including llamas and camels) but also found in cartilaginous fish, consist of a single variable heavy chain domain (VHH) that binds to specific epitopes. Nanobodies have equivalent binding specificity to antigens as antibodies but are more heat- and detergent-stable.

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.

Human TL 1A-transgenic Mouse as a Disease and Therapeutic Model

This technology includes mouse models of TL 1A diseases, such as inflammatory bowel disease and rheumatoid arthritis, to be used as a platform for studying therapeutic agents. The TNF family cytokine TL 1A co-stimulates T-cells through Its receptor and is required for autoimmune pathology driven by diverse T-cell subsets. Blocking TL 1A in mouse models of these diseases is efficacious blocking TL 1A may be useful for therapy of diseases in which TL 1A plays a pathogenic role.

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.

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.