Cotl1-flox Mouse

Cotl1, also known as Coactosin-Like Protein 1, is a cytoskeleton-associated protein belonging to the actin-depolymerizing factor (ADF)/cofilin family [3,4]. It binds to F-actin and is involved in regulating cytoskeletal remodeling, which is crucial for processes like cell migration, adhesion, and signaling [3]. It may also participate in pathways related to tumor progression and oxidative stress response [1,3].

In a study on intracerebral hemorrhage (ICH), machine-learning algorithms integrating bulk and single-cell RNA data showed that Cotl1 was closely associated with high oxidative stress (OS) after ICH. After ICH, Cotl1 might penetrate the brain via monocytes, localize within microglia, and enhance OS activity [1]. In glioblastoma (GBM), Cotl1 had high expression in human GBM tissues, was related to recurrence and prognosis, and promoted cell proliferation in vitro and tumor growth in a xenograft mouse model [2]. Pan-cancer analysis and low-grade glioma (LGG) validation found that Cotl1 was highly expressed in most cancers, correlated with decreased survival in Glioma, Glioblastoma multiforme, and pan-kidney cohorts, and was associated with DNA and RNA stemness, immunological checkpoints, immune infiltration cells, tumor mutation burden (TMB), microsatellite instability (MSI), neoantigen (NEO), and programmed death ligand 1 (PD-L1) [3]. In breast cancer, its expression was higher in cancer tissues than normal tissues, correlated with poor prognosis and immune cell infiltration, and it was involved in immune response [5]. In mouse corticogenesis, overexpression of Cotl1 impaired the migration of early-and late-born neurons, delayed neuronal migration in late-born neurons, and disturbed the morphology of migrating neurons [4]. Further study showed that the Lys 75, Arg 73, and Lys 131 sites of Cotl1 were important for its function in affecting neuronal migration, and overexpression of Cotl1 inhibited the proliferation and mitotic activity of neuronal progenitors (NPs) [6]. Also, in breast cancer, down-regulation of microRNA-30c-5p increased COTL1 expression, which enhanced cell migration ability via COTL1-mediated microfilament arrangement [7].

In conclusion, Cotl1 plays essential roles in various biological processes such as cell migration during development and in cancer-related processes like tumor growth, metastasis, and immune-related events. Its association with oxidative stress in ICH also indicates its significance in neurological injury-related conditions. The findings from these model-based studies, especially in mouse models, have provided valuable insights into Cotl1's functions in different disease areas.