Pfn1-flox Mouse

Pfn1, or Profilin 1, is an actin-binding protein. It regulates actin polymerization, cell proliferation, apoptosis, angiogenesis, and carcinogenesis [2]. It is also involved in neuronal growth and differentiation, membrane trafficking, and regulation of the actin cytoskeleton [6]. Genetic models are valuable for studying Pfn1's role in biological processes and diseases.

In the context of amyotrophic lateral sclerosis (ALS), patients with PFN1 mutations, like the M114V mutation, typically show a phenotype with pedigrees over five cases, an age of onset around 50 years, lower limb onset, and no cognitive impairment [1]. In iPSC-derived microglia harboring ALS-related PFN1 mutations, there are lipid dysmetabolism, autophagy dysregulation, and deficient phagocytosis, indicating a gain-of-toxic function for mutant PFN1 within autophagic and endo-lysosomal pathways [4,5]. In bovine myoblast cells, PFN1 negatively regulates myogenic differentiation via the Cdc42-PAK/JNK pathway [3]. In psoriasis, PFN1 acts as a negative regulator of psoriatic inflammation through the suppression of IκBζ, and its expression can be used as a biomarker for psoriasis severity [2]. In colorectal cancer, the HLA-F-AS1/miR-330-3p/PFN1 axis promotes cancer progression [7]. In the Chinese population, PFN1 gene polymorphisms are associated with bone mineral density (BMD) in males and β-C-Terminal telopeptide of type 1 collagen (β-CTX) in all subjects, and are related to male osteoporotic fractures [8].

In conclusion, Pfn1 is a multifunctional protein involved in various biological processes. Studies using different models, including those related to ALS, psoriasis, myogenesis, cancer, and osteoporosis, have revealed its crucial role in these disease-related biological processes. These findings help in understanding the molecular mechanisms underlying these diseases and may potentially lead to new therapeutic strategies.