Elp1-flox Mouse

Elp1, also known as IKAP, is a core subunit of the Elongator complex. It has been implicated in translational regulation, and is crucial for maintaining genome integrity, as it is involved in pathways like RAD51-mediated homologous recombination repair for DNA double-strand break repair [1].

Elp1 deficiency in mouse models has revealed its significance in multiple biological processes. In mouse embryonic fibroblasts, Elp1 depletion enhanced genomic instability, impaired cell proliferation, and defective HR repair, with reduced RAD51 protein levels due to translational regulation [1]. In mouse models for familial dysautonomia (FD), a disease caused by ELP1 mutations, Elp1 was found essential for the development of neural crest-derived dorsal root ganglia sensory neurons [2]. Also, Elp1 is required for the development of visceral sensory peripheral and central circuitry, as its reduction impairs the entire baroreception and chemoreception circuitry [2]. In cerebellar granule cell progenitors, conditional knockout of Elp1 led to ataxia, smaller cerebella, and fewer granule cells, suggesting its role in the developing cerebellum and in the progressive ataxia phenotypes of FD patients [3].

In conclusion, Elp1 plays essential roles in translational regulation, genome stability, and the development of neural circuits. Mouse models, especially KO and CKO models, have been instrumental in revealing its functions in the context of diseases like familial dysautonomia, providing insights into the molecular mechanisms underlying these disorders and potential therapeutic targets.