Qki-KO Mouse

Qki, also known as Quaking, is a member of the signal transduction and activation of RNA (STAR) family and the heterogeneous nuclear ribonucleoprotein K- (hnRNP K-) homology domain protein family. It has three major alternatively spliced isoforms (QKI-5, QKI-6, QKI-7). Qki is involved in regulating pre-mRNA post-transcriptional processing, intracellular migration, and mRNA stability, playing a crucial role in many biological processes such as myelination, cholesterol biosynthesis, and cell differentiation [5].

In lens-specific Qki-deficient mice, genes associated with cholesterol biosynthesis pathway are downregulated, leading to reduced cholesterol levels in the eye lens and eventually cataracts, suggesting Qki activates Srebp2-mediated cholesterol biosynthesis for maintaining eye lens transparency [1]. Qki depletion in neural stem cells or oligodendrocyte precursor cells in neonatal mice impairs cholesterol biosynthesis and myelinogenesis, as Qki-5 functions as a co-activator of Srebp2 to control cholesterol-related gene transcription in oligodendrocytes [2]. In microglia, deletion of Qk gene severely impairs the clearance of myelin debris, with Qki regulating the RNA stability of genes involved in phagosome formation and maturation [3]. BMSC-specific QKI-deficient mice show an increase in bone mass as QKI inhibits BMSCs osteogenic differentiation by suppressing the Wnt pathway [4].

In conclusion, Qki is essential for multiple biological functions, especially in processes related to myelination, cholesterol metabolism, and cell differentiation. The use of Qki KO/CKO mouse models has revealed its role in diseases such as cataracts, demyelinating diseases, and osteoporosis, providing valuable insights into disease mechanisms and potential therapeutic targets.

References:

1. Shin, Seula, Zhou, Hao, He, Chenxi, Chen, Yiwen, Hu, Jian. 2021. Qki activates Srebp2-mediated cholesterol biosynthesis for maintenance of eye lens transparency. In Nature communications, 12, 3005. doi:10.1038/s41467-021-22782-0. https://pubmed.ncbi.nlm.nih.gov/34021134/

2. Zhou, Xin, Shin, Seula, He, Chenxi, Lan, Fei, Hu, Jian. 2021. Qki regulates myelinogenesis through Srebp2-dependent cholesterol biosynthesis. In eLife, 10, . doi:10.7554/eLife.60467. https://pubmed.ncbi.nlm.nih.gov/33942715/

3. Ren, Jiangong, Dai, Congxin, Zhou, Xin, Chen, Yiwen, Hu, Jian. . Qki is an essential regulator of microglial phagocytosis in demyelination. In The Journal of experimental medicine, 218, . doi:10.1084/jem.20190348. https://pubmed.ncbi.nlm.nih.gov/33045062/

4. Yan, Zhao, Ruan, Banjun, Wang, Shan, Lu, Zifan, Cao, Xiaorui. 2023. RNA-binding Protein QKI Inhibits Osteogenic Differentiation Via Suppressing Wnt Pathway. In Archives of medical research, 54, 102853. doi:10.1016/j.arcmed.2023.102853. https://pubmed.ncbi.nlm.nih.gov/37460362/

5. Chen, Xinyun, Yin, Jianwen, Cao, Dayan, Liu, Ying, Shou, Weinian. 2021. The Emerging Roles of the RNA Binding Protein QKI in Cardiovascular Development and Function. In Frontiers in cell and developmental biology, 9, 668659. doi:10.3389/fcell.2021.668659. https://pubmed.ncbi.nlm.nih.gov/34222237/