Dctn5-KO Mouse

Dctn5, a subunit of the dynein complex, is involved in microtubule-dependent trafficking, which may participate in immune response [1]. In mammals, this process is crucial for various cellular functions, and Dctn5 likely plays an important role in facilitating the docking of motor proteins within this context.

In Chinese tongue sole, two transcript variants of Dctn5 (dctn5_tv1 and dctn5_tv2) were cloned. Dctn5_tv1 was widely distributed with high transcription in immune tissue, and its expression could be up-regulated in multiple tissues after Vibrio harveyi challenge. Recombinant Dctn5_tv1 also showed antimicrobial activity, suggesting its involvement in the immune response to bacterial invasion [1].

In cutaneous melanoma patients, low Dctn5 mRNA expression was associated with favorable overall survival, indicating its potential as a prognostic biomarker [2].

In mice with targeted inactivation of Wwtr1, which led to glomerulocystic kidney disease, the expression of Dctn5 was decreased in the kidneys, suggesting its possible role in maintaining renal cilia integrity [3].

In double-mutant mice with Pink1 ablation and A53T-SNCA overexpression, Dctn5 was up-regulated, reflecting changes in multiple cellular dynamics including microtubular function [4].

In ischemic stroke research, Dctn5 was part of an 8-gene signature with high accuracy for diagnosing ischemic stroke [5].

In a study on mental disorders, knockdown of Dctn5, a bipolar disorder susceptibility gene, disrupted neuronal network physiology in vitro [6].

Additionally, in a genome-wide genetic analysis of exercise intervention dropout, a genetic variant within a linkage disequilibrium block related to Dctn5 gene expression in skeletal muscle was associated with exercise intervention dropout [7].

In summary, Dctn5 is involved in diverse biological processes such as immune response, disease prognosis, renal cilia integrity, neuronal network regulation, and may be related to exercise-related genetic factors. Research on Dctn5 using various models has provided insights into its functions in different disease conditions including melanoma, kidney disease, and ischemic stroke, as well as in mental disorders.

References:

1. Wei, Min, Xu, Wen-Teng, Li, Kun-Ming, Zhao, Fa-Zhen, Chen, Song-Lin. 2018. Cloning, characterization and functional analysis of dctn5 in immune response of Chinese tongue sole (Cynoglossus semilaevis). In Fish & shellfish immunology, 77, 392-401. doi:10.1016/j.fsi.2018.04.007. https://pubmed.ncbi.nlm.nih.gov/29635065/

2. Wang, Qiaoqi, Wang, Xiangkun, Liang, Qian, Li, Dong, Pan, Fuqiang. 2018. Prognostic Value of Dynactin mRNA Expression in Cutaneous Melanoma. In Medical science monitor : international medical journal of experimental and clinical research, 24, 3752-3763. doi:10.12659/MSM.910566. https://pubmed.ncbi.nlm.nih.gov/29864111/

3. Hossain, Zakir, Ali, Safiah Mohamed, Ko, Hui Ling, Hong, Wanjin, Hunziker, Walter. 2007. Glomerulocystic kidney disease in mice with a targeted inactivation of Wwtr1. In Proceedings of the National Academy of Sciences of the United States of America, 104, 1631-6. doi:. https://pubmed.ncbi.nlm.nih.gov/17251353/

4. Gispert, Suzana, Brehm, Nadine, Weil, Jonas, Roeper, Jochen, Auburger, Georg. 2014. Potentiation of neurotoxicity in double-mutant mice with Pink1 ablation and A53T-SNCA overexpression. In Human molecular genetics, 24, 1061-76. doi:10.1093/hmg/ddu520. https://pubmed.ncbi.nlm.nih.gov/25296918/

5. Feng, Bing, Meng, Xinling, Zhou, Hui, Wang, Hao, Zou, Donghua. 2021. Identification of Dysregulated Mechanisms and Potential Biomarkers in Ischemic Stroke Onset. In International journal of general medicine, 14, 4731-4744. doi:10.2147/IJGM.S327594. https://pubmed.ncbi.nlm.nih.gov/34456585/

6. MacLaren, Erik J, Charlesworth, Paul, Coba, Marcelo P, Grant, Seth G N. 2011. Knockdown of mental disorder susceptibility genes disrupts neuronal network physiology in vitro. In Molecular and cellular neurosciences, 47, 93-9. doi:10.1016/j.mcn.2010.12.014. https://pubmed.ncbi.nlm.nih.gov/21440632/

7. Jiang, Rong, Collins, Katherine A, Huffman, Kim M, Siegler, Ilene C, Kraus, William E. . Genome-Wide Genetic Analysis of Dropout in a Controlled Exercise Intervention in Sedentary Adults With Overweight or Obesity and Cardiometabolic Disease. In Annals of behavioral medicine : a publication of the Society of Behavioral Medicine, 58, 363-374. doi:10.1093/abm/kaae011. https://pubmed.ncbi.nlm.nih.gov/38489667/