Relch-KO Mouse

Relch, also known as KIAA1468, is a Rab11-binding protein that plays a crucial role in controlling intracellular cholesterol distribution. It acts as a membrane tether, promoting non-vesicular cholesterol transport from recycling endosomes (REs) to the trans-Golgi network (TGN) by interacting with Rab11-GTP and OSBP [2]. This function is significant as cholesterol transport is essential for maintaining normal cellular functions and membrane homeostasis.

In non-small cell lung cancer (NSCLC), a novel oncogenic fusion variant RELCH-RET has been identified [1,3]. Also, in papillary thyroid carcinoma, a KIAA1468-RET rearrangement was detected, which fuses the RET tyrosine kinase to regulatory domains of KIAA1468 [8]. These fusions might activate oncogenic pathways, contributing to cancer development. In chronic rhinosinusitis with nasal polyposis, RELCH was down-regulated in the nasal lavage fluid compared to the control group, suggesting its potential involvement in the disease's inflammatory and immune-related processes [5]. In pigs, RELCH was identified as a candidate gene for fatness traits through meta-analysis of genome-wide association studies, indicating its possible role in fat deposition [4]. In chickens, RELCH, located on GGA2, was associated with the thermogelled egg yolk trait and might participate in cholesterol-related functions related to this trait [6]. In commercial crossbred Piétrain pigs, RELCH was among the genes on SSC1 that might be associated with body composition traits, though further research is needed to clarify its role [7].

In summary, Relch is mainly known for its role in intracellular cholesterol distribution. However, its fusion with RET in cancer and its differential expression in various diseases like chronic rhinosinusitis, along with its potential association with traits in pigs and chickens, suggest a broader significance in disease development and physiological traits. The identification of these associations through different research models provides valuable insights into the diverse functions of Relch and its potential implications in human health and animal breeding.

References:

1. Myrand, Scott P. . A Novel Oncogenic RET Fusion Variant in NSCLC: RELCH-RET. In Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 16, e95. doi:10.1016/j.jtho.2020.12.018. https://pubmed.ncbi.nlm.nih.gov/34561049/

2. Sobajima, Tomoaki, Yoshimura, Shin-Ichiro, Maeda, Tomomi, Miyoshi, Eiji, Harada, Akihiro. 2018. The Rab11-binding protein RELCH/KIAA1468 controls intracellular cholesterol distribution. In The Journal of cell biology, 217, 1777-1796. doi:10.1083/jcb.201709123. https://pubmed.ncbi.nlm.nih.gov/29514919/

3. Jiang, Huachi, Xiao, Mingzhe, Qi, Chuang, Cai, Shangli, Liu, Feng. . A Novel Oncogenic RET Fusion Variant in Non-Small Cell Lung Cancer: RELCH-RET. In Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 15, e27-e28. doi:10.1016/j.jtho.2019.08.2510. https://pubmed.ncbi.nlm.nih.gov/32127187/

4. Zeng, Haonan, Zhong, Zhanming, Xu, Zhiting, Li, Jiaqi, Zhang, Zhe. 2022. Meta-analysis of genome-wide association studies uncovers shared candidate genes across breeds for pig fatness trait. In BMC genomics, 23, 786. doi:10.1186/s12864-022-09036-z. https://pubmed.ncbi.nlm.nih.gov/36451102/

5. Kashoob, Musallam, Masood, Afshan, Alfadda, Assim A, Alsaleh, Saad, Benabdelkamel, Hicham. 2024. Label-Free Quantitative Proteomics Analysis of Nasal Lavage Fluid in Chronic Rhinosinusitis with Nasal Polyposis. In Biology, 13, . doi:10.3390/biology13110887. https://pubmed.ncbi.nlm.nih.gov/39596842/

6. Zhang, Ruiqi, Li, Xinghua, Ma, Ying, Cheng, Xue, Ning, Zhonghua. 2022. Identification of candidate genomic regions for thermogelled egg yolk traits based on a genome-wide association study. In Poultry science, 102, 102402. doi:10.1016/j.psj.2022.102402. https://pubmed.ncbi.nlm.nih.gov/36610105/

7. Heidaritabar, Marzieh, Bink, Marco C A M, Dervishi, Elda, Huisman, Abe, Plastow, Graham S. 2023. Genome-wide association studies for additive and dominance effects for body composition traits in commercial crossbred Piétrain pigs. In Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie, 140, 413-430. doi:10.1111/jbg.12768. https://pubmed.ncbi.nlm.nih.gov/36883263/

8. Staubitz, Julia Isabelle, Schad, Arno, Springer, Erik, Hartmann, Nils, Musholt, Thomas Johannes. 2018. Novel rearrangements involving the RET gene in papillary thyroid carcinoma. In Cancer genetics, 230, 13-20. doi:10.1016/j.cancergen.2018.11.002. https://pubmed.ncbi.nlm.nih.gov/30466862/