Gatad1-KO Mouse

GATAD1, also known as GATA zinc finger domain containing 1, is a zinc finger domain protein initially identified as a histone 3 trimethylated at lysine 4 (H3K4me3) interactor. It functions as a transcription factor, playing a crucial role in various biological processes including heart development and metabolism regulation [4,6]. It has been associated with pathways related to cell cycle regulation, proliferation, and energy metabolism in different tissues, which are of great biological importance. Genetic models, such as zebrafish and mouse models, have been used to study GATAD1's function [2,4].

In a Gatad1 cardiomyocyte-specific knockout (cKO) mouse model, deletion of Gatad1 in cardiomyocytes did not induce cardiomyopathy during aging up to 18 months of age, nor did it affect the response to pressure overload stress. This suggests that Gatad1 may not be essential for maintaining normal cardiac structure and function in mice under these conditions [4]. In zebrafish, studies of the Gatad1 homologue and generation of gatad1 knock-out fish lines, along with transgenic lines expressing a human DCM GATAD1-S102P mutation, revealed heart failure-like phenotypes under stress conditions, indicating its role in adult-onset autosomal recessive dilated cardiomyopathy [2].

In cancer research, GATAD1 gene amplification and expression were found to be novel independent diagnosis biomarkers for poor outcome in glioma patients. GATAD1 knockdown suppressed glioma cell proliferation both in vitro and in vivo, and it promoted CCND1 gene transcription to accelerate cell cycle transition and proliferation [1]. In thyroid cancer, GATAD1 was overexpressed in recurrent tissue and was identified as a key risk factor for recurrence. Knockdown of GATAD1 inhibited thyroid cancer cell proliferation and arrested cells in the G1 phase [3]. In estrogen receptor-positive breast cancer, GATAD1 was identified as a synthetic lethal target with CDK4/6 inhibitors. GATAD1 promoted cell proliferation by transcriptionally inhibiting p21, and its depletion induced cell cycle arrest [5].

In summary, GATAD1 plays diverse roles in different biological processes and diseases. The use of gene knockout models, such as the Gatad1 cKO mouse model, has provided valuable insights into its function in cardiac development and disease. In cancer, GATAD1 has been implicated in promoting malignancy and recurrence, highlighting its potential as a diagnostic biomarker and therapeutic target. These findings contribute to a better understanding of the molecular mechanisms underlying various diseases and may offer new strategies for treatment [1-5].

References:

1. Zhang, Shanshan, Gao, Min, Yu, Lin. 2019. GATAD1 gene amplification promotes glioma malignancy by directly regulating CCND1 transcription. In Cancer medicine, 8, 5242-5253. doi:10.1002/cam4.2405. https://pubmed.ncbi.nlm.nih.gov/31286678/

2. Yang, Jingchun, Shah, Sahrish, Olson, Timothy M, Xu, Xiaolei. 2016. Modeling GATAD1-Associated Dilated Cardiomyopathy in Adult Zebrafish. In Journal of cardiovascular development and disease, 3, . doi:10.3390/jcdd3010006. https://pubmed.ncbi.nlm.nih.gov/28955713/

3. Wang, Xingquan, Su, Dewang, Wei, Yaqing, Tian, Hao, Wei, Weiwei. . Effect of GATAD1 regulating the SRRM2 gene on recurrence of thyroid tumor and its molecular mechanism. In Gland surgery, 11, 1897-1907. doi:10.21037/gs-22-666. https://pubmed.ncbi.nlm.nih.gov/36654960/

4. Pang, Jing, Zhu, Siting, Shyy, Melody, Gu, Yusu, Fang, Xi. 2024. Loss of GATAD1 in cardiomyocyte does not cause cardiomyopathy in mice. In Journal of molecular histology, 56, 33. doi:10.1007/s10735-024-10297-z. https://pubmed.ncbi.nlm.nih.gov/39641830/

5. Liu, Wenqiang, Zhang, Ruhua, Yu, Xinhao, Kang, Tiebang, Liao, Dan. 2023. CRISPR screen identifies GATAD1 as a synthetic lethal target with CDK4/6 inhibitors in estrogen receptor-positive breast cancer. In Medical oncology (Northwood, London, England), 40, 267. doi:10.1007/s12032-023-02133-3. https://pubmed.ncbi.nlm.nih.gov/37567972/

6. Cai, Yuqing, Yu, Yifan, Zhang, Tianliang, Yan, Wenxiu, Zhao, Jing. 2024. GATAD1 is involved in sphingosylphosphorylcholine-attenuated myocardial ischemia-reperfusion injury by modulating myocardial fatty acid oxidation and glucose oxidation. In Free radical biology & medicine, 227, 166-178. doi:10.1016/j.freeradbiomed.2024.11.054. https://pubmed.ncbi.nlm.nih.gov/39626862/