Ptprn-KO Mouse

Ptprn, encoding protein tyrosine phosphatase receptor type N, lacks protein tyrosine phosphatase activity due to mutations in its intracellular catalytic domains but has acquired new cellular roles in the neuroendocrine system [5]. It is expressed in neuroendocrine cells of the hypothalamus, pituitary gland, pancreas, lung, and intestine, and is involved in regulating intrinsic neuronal excitability, tumor progression, and reproduction-related processes [1,2,3,4,5].

In a knockout mouse model, the knockout of Ptprn in hippocampal granule cells led to augmented NaV1.2-mediated sodium currents and higher intrinsic excitability, increasing seizure susceptibility. Conversely, adeno-associated virus-mediated delivery of Ptprn in the dentate gyrus region decreased intrinsic excitability and reduced seizure susceptibility, indicating its role in regulating seizure susceptibility [1]. In female rats, knockdown of Ptprn-2 (a related polypeptide-encoding gene) regulated levels of puberty-related genes in the hypothalamus, serum reproductive hormones, and the morphology of ovarian and gonadotropin cells, delaying the onset of puberty [4]. In glioma, knockdown of Ptprn reduced cell proliferation and migration, and decreased tumor growth in a mouse xenograft model, while its overexpression had the opposite effects [7]. In lung adenocarcinoma, overexpression of Ptprn promoted cell migration, was related to metastasis, and suppressed NK cell cytotoxicity [6]. In low-grade glioma, Ptprn expression was decreased compared to normal brain tissue, and high expression was associated with better overall survival, also correlating with tumor immune infiltration [2]. Additionally, in glioblastoma, Ptprn was part of a cuproptosis-related prognostic model [3].

In conclusion, Ptprn plays essential roles in regulating intrinsic neuronal excitability, puberty onset, and tumor-related processes such as proliferation, metastasis, and immune infiltration. Gene knockout or knockdown models in mice and rats have significantly contributed to understanding its functions in epilepsy, puberty-related disorders, and various cancers including glioma, glioblastoma, and lung adenocarcinoma.

References:

1. Wang, Yifan, Yang, Hui, Li, Na, Tian, Xin, Huang, Zhuo. 2024. A Novel Ubiquitin Ligase Adaptor PTPRN Suppresses Seizure Susceptibility through Endocytosis of NaV1.2 Sodium Channels. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2400560. doi:10.1002/advs.202400560. https://pubmed.ncbi.nlm.nih.gov/38874331/

2. Li, Peng, Chen, Fanfan, Yao, Chen, Zhang, Bei, Zheng, Zelong. 2022. PTPRN Serves as a Prognostic Biomarker and Correlated with Immune Infiltrates in Low Grade Glioma. In Brain sciences, 12, . doi:10.3390/brainsci12060763. https://pubmed.ncbi.nlm.nih.gov/35741647/

3. Zhang, Bohong, Xie, Lin, Liu, Jiahao, Liu, Anmin, He, Mingliang. 2023. Construction and validation of a cuproptosis-related prognostic model for glioblastoma. In Frontiers in immunology, 14, 1082974. doi:10.3389/fimmu.2023.1082974. https://pubmed.ncbi.nlm.nih.gov/36814929/

4. Kang, Tiezhu, Ye, Jing, Qin, Ping, Wang, Juhua, Fang, Fugui. 2021. Knockdown of Ptprn-2 delays the onset of puberty in female rats. In Theriogenology, 176, 137-148. doi:10.1016/j.theriogenology.2021.09.029. https://pubmed.ncbi.nlm.nih.gov/34607132/

5. Stojilkovic, Stanko S, Sokanovic, Srdjan J, Constantin, Stephanie. 2025. What is known and unknown about the role of neuroendocrine genes Ptprn and Ptprn2. In Frontiers in endocrinology, 16, 1531723. doi:10.3389/fendo.2025.1531723. https://pubmed.ncbi.nlm.nih.gov/39926347/

6. Song, Xinyue, Jiao, Xue, Yan, Han, Zhao, Lin, Wei, Minjie. 2021. Overexpression of PTPRN Promotes Metastasis of Lung Adenocarcinoma and Suppresses NK Cell Cytotoxicity. In Frontiers in cell and developmental biology, 9, 622018. doi:10.3389/fcell.2021.622018. https://pubmed.ncbi.nlm.nih.gov/34150744/

7. Wang, Dong, Tang, Fan, Liu, Xi, Zhuo, Jie, Wang, Bo. 2021. Expression and Tumor-Promoting Effect of Tyrosine Phosphatase Receptor Type N (PTPRN) in Human Glioma. In Frontiers in oncology, 11, 676287. doi:10.3389/fonc.2021.676287. https://pubmed.ncbi.nlm.nih.gov/34557405/