Elavl3-flox Mouse

Elavl3, also known as neuronal Elav-like 3 or HuC, is an RNA-binding protein. It belongs to the nElavl family and is highly expressed in the adult brain. Elavl3 regulates RNA stability, alternative splicing, and polyadenylation site choice, which are crucial for axonal and synaptic structures, as well as neuronal differentiation, maturation, and polarity regulation [2,3,5].

In Elavl3-/-mice, there are slowly progressive motor deficits leading to severe cerebellar ataxia, with swollen axons in Purkinje cells, disruption of synaptic formation, and deficits in axonal transport and neuronal polarity [2]. Also, in these mice, the alternative splicing of AnkyrinG exon 34 is misregulated, affecting neuronal polarity [3]. In neuroendocrine prostate cancer, ELAVL3 is specifically upregulated, forming a positive feedback loop with MYCN. Pharmacological inhibition of ELAVL3 suppresses tumor growth in mouse models [1]. In neuroblastoma, targeted silencing of ELAVL3 down-regulates MYCN gene expression and reduces malignancy [4].

In conclusion, Elavl3 is essential for maintaining axonal homeostasis, regulating neuronal polarity, and is involved in the development of certain cancers. Studies using Elavl3 knockout mouse models have provided valuable insights into its functions in normal neuronal processes and disease conditions such as neurodegenerative diseases and cancers [1,2,3,4].