Elp1-KO Mouse

Elp1, also known as IKBKAP, is the largest subunit of the evolutionarily conserved Elongator complex. This complex is involved in translational elongation through tRNA modifications at the wobble (U34) position, which is crucial for maintaining normal cellular functions [3]. Genetic models, especially mouse models, have been instrumental in studying Elp1's function.

Mutations in Elp1 cause familial dysautonomia (FD), a sensory and autonomic neuropathy. Mouse models with Elp1 knockout (KO) or conditional knockout (CKO) have shown that Elp1 is essential for the normal development of neural crest-derived dorsal root ganglia sensory neurons, as well as for the development of visceral sensory peripheral and central circuitry. In Elp1-deficient mouse embryonic fibroblasts (MEFs), genomic instability is enhanced, and DNA double-strand break repair is impaired due to reduced RAD51 protein levels, indicating its role in maintaining genome integrity [1,2]. In a mouse model of FD, correction of mutant ELP1 splicing by kinetin rescued neurological phenotypes, highlighting the importance of normal ELP1 splicing [4]. In trigeminal ganglion development, Elp1 is required for proper axon outgrowth, target innervation, and survival of nociceptors, as shown by Elp1 knockdown in chick trigeminal placode cells and Elp1 CKO in mice [5,6,8]. Also, loss of Elp1 in cerebellar granule cell progenitors in mice led to ataxia, demonstrating its importance in cerebellar development [7]. In addition, Elp1 is required for normal enteric nervous system development and maintenance and for gut epithelium homeostasis in mice [9].

In conclusion, Elp1 is vital for multiple biological processes, including neuronal development, genome stability, and gut homeostasis. Mouse models, especially KO and CKO models, have been crucial in revealing its roles in diseases like familial dysautonomia, providing insights into the disease mechanisms and potential therapeutic strategies.