Ankrd16-KO Mouse

Ankrd16, encoding a vertebrate-specific protein with ankyrin repeats, plays a crucial role in maintaining translational fidelity by acting as an amino-acid-accepting co-regulator of tRNA synthetase editing. It binds directly to the catalytic domain of alanyl tRNA synthetase (AlaRS), and is involved in a pathway that prevents the mis-charging of tRNAAla with serine, thus precluding serine misincorporation in nascent peptides [1].

In Aarssti/sti mutant mice, which have a mutation in the editing domain of AlaRS leading to increased production of serine-mischarged tRNAAla and cerebellar Purkinje cell degeneration, Ankrd16 acts epistatically with the Aars sti mutation to attenuate neurodegeneration. Deletion of Ankrd16 in the brains of these mice causes widespread protein aggregation and neuron loss, revealing its essential role in preventing pathologies arising from editing defects [1].

In conclusion, Ankrd16 is vital for translational fidelity through its interaction with AlaRS. Gene knockout experiments in mouse models have shown its significance in preventing neurodegeneration caused by editing-defective tRNA synthetase, highlighting its importance in understanding the mechanisms underlying certain neurological pathologies. Additionally, Ankrd16 has been associated with IgA nephropathy in Koreans as a potential genetic susceptibility locus, and with breast cancer subtypes in white and African-American women, indicating its possible roles in these diseases as well [2,3].

References:

1. Vo, My-Nuong, Terrey, Markus, Lee, Jeong Woong, Schimmel, Paul, Ackerman, Susan L. 2018. ANKRD16 prevents neuron loss caused by an editing-defective tRNA synthetase. In Nature, 557, 510-515. doi:10.1038/s41586-018-0137-8. https://pubmed.ncbi.nlm.nih.gov/29769718/

2. Jeong, Kyung Hwan, Kim, Jin Sug, Lee, Yu Ho, Lee, Sang Ho, Kim, Yeong Hoon. 2019. Genome-wide association study identifies new susceptible loci of IgA nephropathy in Koreans. In BMC medical genomics, 12, 122. doi:10.1186/s12920-019-0568-6. https://pubmed.ncbi.nlm.nih.gov/31426789/

3. O'Brien, Katie M, Cole, Stephen R, Engel, Lawrence S, Herring, Amy H, Millikan, Robert C. 2013. Breast cancer subtypes and previously established genetic risk factors: a bayesian approach. In Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 23, 84-97. doi:10.1158/1055-9965.EPI-13-0463. https://pubmed.ncbi.nlm.nih.gov/24177593/