Laptm4b-KO Mouse

Laptm4b, or Lysosome-associated protein transmembrane-4β, is a gene with significant biological importance. It contains four transmembrane domains and is involved in multiple key biological functions. Laptm4b is associated with pathways such as mTORC1 signaling [1,4,6], PI3K/AKT signaling [3], and Wnt1/c-Myc/β-catenin pathway [5], and is crucial for processes like autophagy, cell proliferation, invasion, metastasis, apoptosis resistance, and drug resistance [2,3]. Genetic models, especially knockout (KO) mouse models, have been instrumental in studying its functions.

In myocardial ischemia/reperfusion injury, Laptm4b-knockout (Laptm4b-/-) mice showed increased infarct size and lactate dehydrogenase release, along with impaired autophagic flux due to over-activation of mTORC1 and repression of TFEB [1]. In non-small cell lung cancer, Laptm4b knockout led to a significant enrichment of ferroptosis and associated metabolic alterations as Laptm4b normally counteracts ferroptosis by suppressing the ubiquitin-proteasome degradation of SLC7A11 [4].

In conclusion, Laptm4b plays essential roles in regulating autophagy, cell survival, and metabolism through its involvement in multiple signaling pathways. Studies using Laptm4b KO mouse models have provided valuable insights into its functions in diseases such as myocardial ischemia/reperfusion injury and non-small cell lung cancer, highlighting its potential as a therapeutic target.

References:

1. Gu, Shanshan, Tan, Jiliang, Li, Qiang, Cao, Nan, Yang, Huang-Tian. 2020. Downregulation of LAPTM4B Contributes to the Impairment of the Autophagic Flux via Unopposed Activation of mTORC1 Signaling During Myocardial Ischemia/Reperfusion Injury. In Circulation research, 127, e148-e165. doi:10.1161/CIRCRESAHA.119.316388. https://pubmed.ncbi.nlm.nih.gov/32693673/

2. Meng, Y, Wang, L, Chen, D, Zhou, R, Zhang, Q-Y. 2016. LAPTM4B: an oncogene in various solid tumors and its functions. In Oncogene, 35, 6359-6365. doi:10.1038/onc.2016.189. https://pubmed.ncbi.nlm.nih.gov/27212036/

3. Ji, Xiaokun, Ma, Hua, Du, Yun. 2022. Role and mechanism of action of LAPTM4B in EGFR-mediated autophagy. In Oncology letters, 23, 109. doi:10.3892/ol.2022.13229. https://pubmed.ncbi.nlm.nih.gov/35242237/

4. Yan, Ruyu, Liu, Dan, Guo, Hongjuan, Blom, Tomas, Zhou, Kecheng. 2024. LAPTM4B counteracts ferroptosis via suppressing the ubiquitin-proteasome degradation of SLC7A11 in non-small cell lung cancer. In Cell death & disease, 15, 436. doi:10.1038/s41419-024-06836-x. https://pubmed.ncbi.nlm.nih.gov/38902268/

5. Wang, Haojun, Zhou, Quanwei, Xie, Ding Fang, Yang, Tongwang, Wang, Wei. 2024. LAPTM4B-mediated hepatocellular carcinoma stem cell proliferation and MDSC migration: implications for HCC progression and sensitivity to PD-L1 monoclonal antibody therapy. In Cell death & disease, 15, 165. doi:10.1038/s41419-024-06542-8. https://pubmed.ncbi.nlm.nih.gov/38388484/

6. Dichlberger, Andrea, Zhou, Kecheng, Bäck, Nils, Ikonen, Elina, Blom, Tomas. 2020. LAPTM4B controls the sphingolipid and ether lipid signature of small extracellular vesicles. In Biochimica et biophysica acta. Molecular and cell biology of lipids, 1866, 158855. doi:10.1016/j.bbalip.2020.158855. https://pubmed.ncbi.nlm.nih.gov/33181324/