RESOURCES

RESEARCH AREA: Autoimmune Cardiovascular Disease Cell and Gene Therapy Infectious Disease Metabolism Neurology Oncology Other Rare Disease

November 20, 2024

BALB/C-hIL12RB1/hIL12RB2 Serves as a Robust Mouse Model to Evaluate Novel Human IL-12 Therapeutics

Interleukin-12 (IL-12) is a multifunctional cytokine predominantly produced by activated inflammatory cells. IL-12 plays a pivotal role in orchestrating the immune response of Th1 cells, promoting interferon (IFN-γ) production, and enhancing the activation of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Preclinical investigations have highlighted IL-12's ability to stimulate T cells and NK cells within the tumor microenvironment, leading to potent anti-tumor effects, thereby positioning IL-12 as a promising therapeutic target. GemPharmatech developed a novel mouse model expressing human IL-12RB1 and IL-12RB2 (BALB/c-hIL-12RB1/hIL-12RB2), providing a powerful tool to evaluate novel human IL-12 therapeutics.
November 20, 2024

Phenotypic Validation of Humanized IgA1 and CD89 Transgenic Mice as a Model for IgA Nephropathy-Like Autoimmune Disease

The etiology of IgA nephropathy (IgAN) remains only partly understood, but the presence of IgA antibodies together with the myeloid IgA receptor FcαRI/CD89 complexes in the circulation of patients is considered a specific pathogenic factor for mesangial deposition. The absence of a CD89 ortholog in rodents, coupled with the differences in the IgA systems between humans and mice, further hinders exploration of IgAN pathogenesis. To better understand the pathogenesis of IgAN, we developed a transgenic mouse model expressing human IgA1 and CD89 (B6-Cd14-hCD89/hIGHA1), in which CD89 is expressed under the control of an endogenous murine CD14 promoter on blood and tissue monocytes/macrophages. This results in a relevant preclinical mouse model useful for the evaluation of CD89 and IgA1-targeted therapies. The B6-Cd14-hCD89/hIGHA1 mice exhibited an IgAN-like phenotype. This novel model can contribute significantly to unraveling the mechanisms underlying IgAN and provide a clinically relevant mouse model for evaluating novel therapeutics against IgAN.
November 20, 2024

Humanized BAFF Transgenic Mice Develop Autoimmune Manifestations

B-cell-activating factor (BAFF) plays a critical role in B cell survival, and its elevated expression can contribute to the presence of autoreactive B cells, potentially leading to autoimmune conditions like Systemic Lupus Erythematosus (SLE). To deepen our understanding of these mechanisms, GemPharmatech developed a transgenic mouse model featuring human BAFF overexpression. This model offers insights into SLE pathogenesis and serves as a relevant preclinical tool for assessing therapies targeting B cells.
August 26, 2024

Establishment of Bleomycin-Induced Scleroderma Mouse Model on HSC-NCG-IL15 Humanized Mice

Systemic sclerosis (SSc), also known as scleroderma, is a rare autoimmune connective tissue disorder associated with significant morbidity and mortality. Numerous studies have reported the involvement of the immune system, particularly T, B, and NK cell-mediated responses, in SSc pathogenesis. However, the underlying mechanisms remain elusive. Therefore, the development of a humanized immune system reconstitution mouse model is essential for advancing such investigations. In this study, we utilized Bleomycin (BLM) to induce a scleroderma mouse model in HSC-NCG-IL15 mice.
August 26, 2024

A Novel Humanized Rheumatoid Arthritis Mice Model for Therapeutic Assessment

Rheumatoid Arthritis is caused by a complex immune system disorder. In this study, we developed a RA disease model induced in humanized HSC-NCG-M mice to mimic manifestations seen in patients. This model incorporates human innate and adaptive immune cells, providing valuable insights for studying RA mechanisms and evaluating drug efficacy.
July 27, 2024

Tirzepatide and Efruxifermin Demonstrate Therapeutic Benefits for NASH in a Preclinical Metabolic Syndrome Animal Model, B6-Alms1-del Mice

To assess treatments for MASLD and its severe form, MASH, GemPharmatech developed the B6-Alms1-del mouse model. Previous studies have shown that this model spontaneously develops metabolic syndrome (including obesity, hyperglycemia, hyperinsulinemia, and dyslipidemia) and MASH, with these conditions mitigated by treatment with the GLP-1R agonist semaglutide. In this study, we evaluated two additional promising anti-MASH agents, Tirzepatide (a GLP-1R & GIPR dual agonist) and Efruxifermin (an FGF21 analog, also known as AKR001), using the B6-Alms1-del MASH animal model.
July 27, 2024

B6-Chr1KM: A Novel Mouse Model for Spontaneous NASH Research

Human MASH (metabolic dysfunction-associated steatohepatitis) involves complex genetic and environmental factors. Current mouse models fail to fully imitate human MASH due to limited genetic diversity and disease susceptibility in inbred mice. Wild mice, with greater genetic diversity, offer potential for more accurate modeling of complex traits like MASH. We developed 8 chromosome 1 (Chr1) substitution strains to explore more appropriate mouse models for MASH research, focusing on lipid metabolism-related gene loci. Table 1 summarizes phenotypic screening results of these strains on a chow diet.
July 07, 2024

A mouse model for Inflammatory Bowel Disease based on DSS-induced NCG-M mice reconstituted with human Hematopoietic Stem Cells

For the past 20 years, numerous murine models of colitis have been developed to study human Inflammatory Bowel Disease (IBD) mechanistically. However, these neither reflect the heterogeneous symptoms observed in the IBD-affected population nor can be used to test the efficacy of clinical drugs which show no cross-reactivity with murine targets. In an attempt to overcome these problems, we have successfully developed a colitis mouse model that relies on DSS-induced NCG-M mice reconstituted with human hematopoietic stem cells (HSCs) from healthy individuals. We also observed a significant pharmacodynamic effect of Mesalazine and a small molecular inhibitor in this colitis model.
June 30, 2024

The GPT hSOD1 G93A Mouse Model Can Recapitulate Progressive ALS-Like Phenotypes

GemPharmatech (GPT) generated the SOD1 transgenic mouse strain (C57BL/6JGpt-Tg(hSOD1 G93A,hSOD1)6J/Gpt) to mimic ALS-like phenotypes in an animal model.

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