品系特征：

BRGSF-HIS小鼠可重建出所有主要的人造血干细胞分化亚群：包括人源淋巴系细胞 （e.g., T、B、NK细胞）、人源髓系细胞组分（e.g., 传统的树突状细胞 (cDCs)、浆细胞样树突状细胞 (pDCs)、单核/巨噬细胞）。经hFlt3L处理可进一步促进人源免疫细胞，特别是髓系细胞组分的发育。

品系优势：

• CD34⁺HSC可重建出主要的人源淋巴系和髓系细胞，真实模拟人体免疫环境；
• 重建的人源细胞长效存在，实验窗口期长；
• rag2基因敲除（非prkdcSCID基因突变），小鼠具有较高的辐照耐受性；
• 补体系统功能健全，是研究补体依赖的细胞毒性（CDC）的有力工具；
• 经长期观察，小鼠未出现体重异常及贫血现象。

应用场景：

• CDX，PDX模型构建；
• 抗体、ADC药物药效学评估；
• 疫苗研发与验证；
• 自免与炎症研究；  
• 安全性评估（细胞因子风暴CRS）;
• 补体相关机制及治疗研究；
• 移植物抗宿主病相关研究 (GvHD)；
• 人源淋巴系与髓系细胞发育研究。

验证信息：

（1）人源免疫细胞重建检测(外周血)：

BRGSF-HIS小鼠HSC免疫重建12周，hCD45⁺细胞占比超过60%，且重建效果稳定（观察时间大于31周）。重建细胞主要为淋巴系细胞（T细胞，B细胞），髓系细胞含量较少。

（2）hFlt3L(i.p.)可促进人源免疫细胞，特别是髓系细胞组分的发育：

每2-3天进行hFlt3L注射（持续1周），外周血中单核细胞 (Monocytes)，树突状细胞(pDC and cDC) 含量明显升高，同时检测到NK细胞含量也有所增加。各细胞 (Monocytes/pDC/cDC/NK) 可经hFlt3L再次注射被重新刺激发育。

更多详细数据请联系我们：联系我们 - 基锘威 - genOway (my3w.com)

案例

1. Homeostasis of monocytes and lung interstitial macrophages is regulated by collagen domain-binding receptor LAIR1 in vivo
2. Predictive in vivo evaluation of immunotherapy efficacy: tHIS is a reliable model
3. Deciphering high-dose IL-2 toxicity in reconstituted HIS mice

评论

1. BRGSF-HIS: genOway’s mouse model to evaluate the pathogenesis of Staphylococcus aureus Panton-Valentine leukocidin in acute implant-associated osteomyelitis
2. Myeloid and dendritic cells enhance therapeutics-induced cytokine release syndrome features in humanized BRGSF-HIS preclinical model
3. Targeting myeloid cells in the tumor microenvironment in BRGSF-HIS mice
4. Assessing T-cell engagers efficacy in vivo: Versatility of BRGSF-HIS mice
5. Expression of druggable myeloid targets in the BRGSF-HIS preclinical model
6. Functional human myeloid compartment in BRGSF-HIS preclinical model
7. Assessing T-cell engagers in vivo: How BRGSF-HIS mice can help
8. Challenging the predictability of preclinical models for assessment of T-cell engagers
9. Targeting tumor-associated myeloid cells: The new grail in immuno-oncology?
10. Immunotherapy efficacy assessment and metastases studies: tHIS model is highly permissive to engraftment
11. Cytokine release syndrome (CRS)
12. Tumor grafts in preclinical research: Models, models, overall, who is the fittest of them all?
13. Define “humanized”: two mouse models helping produce cancer immunotherapies
14. Part 1: Toward a better effective preclinical model in immuno-oncology
15. Part 2: BRGSF, a new immunodeficient model for immuno-oncology studies
16. Part 3: BRGSF-HIS, a new human immune system mouse model for immuno-oncology studies

已发文献

1. VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response
2. Myeloid and dendritic cells enhance therapeutics-induced cytokine release syndrome features in humanized BRGSF-HIS preclinical model
3. Staphylococcus aureus Panton-Valentine Leukocidin worsens acute implant-associated osteomyelitis in humanized BRGSF mice
4. Imiquimod induces skin inflammation in humanized BRGSF mice with limited human immune cell activity
5. Frontline Science: Exhaustion and senescence marker profiles on human T cells in BRGSF-A2 humanized mice resemble those in human samples

海报

1. Tumor cell line-derived xenograft subtype shapes tumor microenvironment composition in BRGSF-HIS mice
2. Cell-depleting agents assessment in preclinical models
3. Myeloid cells' contribution is key in CRS pathophysiology induced by T-cell engagers in BRGSF-HIS model
4. Functional human myeloid cells in BRGSF-HIS humanized mice enable myeloid-directed therapy assessment
5. CD3 humanized mouse models as validated tools to assess immune-related adverse events of T-cell engagers
6. Anti-VISTA agents profiling: complementarity of BRGSF-HIS and hVISTA Knock-in as preclinical models for immunotherapies
7. Translatable preclinical mouse models for assessment of T-cell engager-induced CRS