B6-hCD28 Mouse
製品名
B6-hCD28 Mouse
製品ID
C001817
系統名
C57BL/6NCya-Cd28tm1(hCD28)/Cya
背景情報
C57BL/6NCya
状況
このマウス系統を論文で使用する場合は、「B6-hCD28 Mouse（カタログ番号C001817）はサイアジェンから購入しました。」と引用してください。
製品タイプ
年齢
遺伝子型
性別
数量
遺伝子名
遺伝子別名
Tp44
NCBI ID
染色体
Chr 2
MGI ID
さらに
系統詳細
The CD28 gene encodes the CD28 protein, a crucial co-stimulatory receptor found primarily on T cells, with expression typically on over 80% of human CD4+ T cells and about 50% of CD8+ T cells. It is also expressed, though less understood, on bone marrow stromal cells, plasma cells, neutrophils, and eosinophils, and some B cells [1]. The encoded protein is a disulfide-linked homodimer belonging to the immunoglobulin superfamily, serving as a receptor for CD80 (B7-1) and CD86 (B7-2) found on antigen-presenting cells (APCs) [2]. Its primary function is to provide essential "second signals" for optimal T cell activation, proliferation, survival, and differentiation (including cytokine production like IL-2, IL-4, IL-10, and T-helper type-2 development), complementing the T-cell receptor (TCR) signal. Without CD28 engagement, TCR stimulation often leads to T cell anergy (unresponsiveness) [3]. The gene's expression can be modulated, with some antigen-experienced T cells losing CD28 expression, particularly with age or during chronic infections, leading to a "senescent" or "exhausted" phenotype. Dysregulation of CD28 signaling is implicated in various associated diseases, including autoimmune disorders such as rheumatoid arthritis, Sjogren's syndrome, and systemic sclerosis, as well as in transplant rejection, certain cancers (e.g., T-cell lymphomas, acute myeloid leukemia, breast cancer), and chronic infections like HIV, where its downregulation by viral proteins can impair T cell function [4].
The B6-hCD28 mouse is a humanized model, constructed by replacing the mouse Cd28 endogenous extracellular domain (aa.20~150) with the human CD28 extracellular domain (aa.19~152). The murine signal peptide (aa.1~19) and aa.151~218 are preserved. B6-hCD28 mice can be used for research into the pathogenesis of autoimmune disorders such as rheumatoid arthritis, Sjogren's syndrome, and systemic sclerosis, as well as in transplant rejection, certain cancers (e.g., T-cell lymphomas, acute myeloid leukemia, breast cancer), and chronic infections like HIV. They are also useful for the screening, development, and safety evaluation of CD28-targeted drugs.
参考文献
Esensten JH, Helou YA, Chopra G, Weiss A, Bluestone JA. CD28 Costimulation: From Mechanism to Therapy. Immunity. 2016 May 17;44(5):973-88.
Leddon SA, Fettis MM, Abramo K, Kelly R, Oleksyn D, Miller J. The CD28 Transmembrane Domain Contains an Essential Dimerization Motif. Front Immunol. 2020 Jul 16;11:1519.
Ciesielska-Figlon K, Lisowska KA. The Role of the CD28 Family Receptors in T-Cell Immunomodulation. Int J Mol Sci. 2024 Jan 20;25(2):1274.
Nga HT, Nguyen TL, Yi HS. T-Cell Senescence in Human Metabolic Diseases. Diabetes Metab J. 2024 Sep;48(5):864-881.
系統作製戦略
The mouse Cd28 endogenous extracellular domain was replaced with the human CD28 extracellular domain.
Figure 1. Gene editing strategy of B6-hCD28 mice.
適用分野
CD28-targeted drug screening, development, and evaluation;
Research on the pathological mechanisms and therapeutic approaches of autoimmune disorders such as rheumatoid arthritis, Sjogren's syndrome, and systemic sclerosis;
Research on the transplant rejection;
Research on the pathological mechanisms and therapeutic approaches of certain cancers;
Research on the pathological mechanisms and therapeutic approaches of chronic infections like HIV.
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