Anxa11-flox Mouse

Anxa11, encoding a Ca2+-dependent phospholipid-binding protein, has functions related to intracellular Ca2+ homeostasis, stress granule dynamics, and serves as a molecular tether between RNA granules and lysosomes for long-distance RNA transport [3,5]. It is involved in pathways like protein-lipid phase coupling on lysosomal membranes [4].

Mutations in Anxa11 are associated with various neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), corticobasal syndrome, and multisystem proteinopathy [1,3-5,9]. For example, the P93S variant in Anxa11 dysregulates TDP-43, leading to decreased lysosome colocalization, neuritic RNA, and nuclear TDP-43, and is pathogenic for corticobasal syndrome [1,2]. ALS-associated mutations in Anxa11 can cause abnormal protein aggregation, dysregulation of calcium homeostasis, and defects in stress granule disassembly [3].

In conclusion, Anxa11 is crucial for maintaining normal cellular functions related to RNA transport, calcium homeostasis, and stress granule dynamics. Research on Anxa11-associated mutations in genetic models has revealed its significant role in neurodegenerative disease pathogenesis, providing insights into potential disease mechanisms and therapeutic targets for these disorders.