Dram2-KO Mouse

DRAM2, short for Damage-regulated autophagy modulator 2, is associated with autophagy processes. It is part of the DRAM family proteins, which are known to induce autophagy. Autophagy is a crucial cellular process involved in maintaining cellular homeostasis, recycling cellular components, and responding to stress [1,2,3,6].

In non-small cell lung cancer (NSCLC), DRAM2 acts as an oncogene. Its overexpression promotes cell metastasis and proliferation, while knockdown has the opposite effect. DRAM2 expression is negatively correlated with p53 expression, and it influences the expression of various cell migration and cell cycle-related factors [1]. In the context of retinopathy, pathogenic variants in DRAM2 cause a rare autosomal recessive retinal dystrophy, known as CORD21. Retinal cells from CORD21 patients show abnormalities in lipid metabolism, autophagic flux, lysosomal content accumulation, and reduced lysosomal enzyme activity [2,3]. In bladder transitional cell carcinoma, up-regulation of DRAM2 promotes tolerance to gemcitabine, and down-regulation can rescue the sensitivity of gemcitabine-resistant cells to the drug [4].

In summary, DRAM2 plays a significant role in autophagy-related biological processes. Its dysregulation is associated with multiple diseases, especially NSCLC, retinopathy, and bladder cancer. Although a Dram2 knockout mouse model did not show overt retinal degeneration, further research is needed to fully understand the mechanisms underlying DRAM2-related diseases, especially those in the retina [2,3,5].

References:

1. Wudu, Muli, Ren, Hongjiu, Hui, Linping, Dao, Runa, Qiu, Xueshan. 2019. DRAM2 acts as an oncogene in non-small cell lung cancer and suppresses the expression of p53. In Journal of experimental & clinical cancer research : CR, 38, 72. doi:10.1186/s13046-019-1068-4. https://pubmed.ncbi.nlm.nih.gov/30755245/

2. Krašovec, Tjaša, Volk, Marija, Šuštar Habjan, Maja, Vidović Valentinčič, Nataša, Fakin, Ana. 2022. The Clinical Spectrum and Disease Course of DRAM2 Retinopathy. In International journal of molecular sciences, 23, . doi:10.3390/ijms23137398. https://pubmed.ncbi.nlm.nih.gov/35806404/

3. Tsikandelova, Rozaliya, Galo, Eldo, Cerniauskas, Edvinas, Kurzawa-Akanbi, Marzena, Lako, Majlinda. 2024. Retinal cells derived from patients with DRAM2-dependent CORD21 dystrophy exhibit key lysosomal enzyme deficiency and lysosomal content accumulation. In Stem cell reports, 19, 1107-1121. doi:10.1016/j.stemcr.2024.06.002. https://pubmed.ncbi.nlm.nih.gov/38964324/

4. Azhati, Baihetiya, Maolakuerban, Naibijiang, Ma, Tao, Li, Xiaodong, Rexiati, Mulati. 2020. Up-regulation of DRAM2 promotes tolerance of bladder transitional cell carcinoma to gemcitabine. In Archives of medical science : AMS, 16, 1207-1217. doi:10.5114/aoms.2020.93748. https://pubmed.ncbi.nlm.nih.gov/32864010/

5. Sun, Kuanxiang, Chen, Junyao, Fan, Yudi, Liu, Wenjing, Zhu, Xianjun. 2024. Lack of retinal degeneration in a Dram2 knockout mouse model. In Vision research, 226, 108509. doi:10.1016/j.visres.2024.108509. https://pubmed.ncbi.nlm.nih.gov/39520804/

6. Zhang, Jinjin, Wang, Haixia, Chen, Hongbin, Lv, Changjun, Song, Xiaodong. 2022. ATF3 -activated accelerating effect of LINC00941/lncIAPF on fibroblast-to-myofibroblast differentiation by blocking autophagy depending on ELAVL1/HuR in pulmonary fibrosis. In Autophagy, 18, 2636-2655. doi:10.1080/15548627.2022.2046448. https://pubmed.ncbi.nlm.nih.gov/35427207/