Havcr2-flox Mouse

Havcr2, also known as TIM-3 (T cell immunoglobulin and mucin domain 3), is a gene encoding a cell surface protein that acts as a negative regulator in the immune system. TIM-3 binds to ligands like galectin-9, Psdter, HMGB1, and Ceacam-1, and is involved in immune regulation pathways, playing a crucial role in autoimmune diseases, chronic viral infections, and tumors [2].

Germline HAVCR2 mutations have been associated with various diseases. For instance, they are linked to subcutaneous panniculitis-like T-cell lymphoma (SPTCL) leading to Hemophagocytic lymphohistiocytosis (HLH), and can cause HLH even without lymphoma [1]. A young male patient with a homozygous c.245 A > G p.Tyr82Cys pathogenic variant in HAVCR2 gene had recurrent myocarditis, suggesting that TIM-3 deficiency due to this mutation is associated with autoinflammatory symptoms [3]. Also, male sex and younger age are associated with HLH in patients with HAVCR2 mutations [4]. Ruxolitinib, targeting inflammatory cytokines, shows excellent efficacy in treating HAVCR2 mutation-associated HLH and panniculitis manifestations, indicating an inflammatory rather than neoplastic nature of the disease [5].

In conclusion, Havcr2 is essential in immune regulation, and its mutations are associated with diseases like HLH, SPTCL, and recurrent myocarditis. The study of HAVCR2 through genetic models, especially in understanding the role of its mutations, provides insights into the pathogenesis of these diseases, which may help develop new treatment strategies.