Park7-KO Mouse

PARK7, also known as DJ-1, is a multifunctional protein. It acts as an antioxidant and oxidative stress sensor, involved in neuroprotective mechanisms, mitochondrial homeostasis, regulation of apoptosis, chaperone-mediated autophagy, and dopamine homeostasis by regulating various signaling pathways, transcription factors, and molecular chaperone functions [1]. It has been linked to the pathogenesis of Parkinson's disease (PD), and also has implications in gut-brain axis diseases, making it a potential therapeutic target in these disease areas [1,2].

In Parkinson's disease, loss-of-function mutations in PARK7 account for approximately 1% of all recessively inherited early-onset PD occurrences [1]. PARK7-deficient mice experience aggravated kidney tissue damage, dysfunction, enhanced tubular apoptosis and inflammation in endotoxic acute kidney injury models, suggesting PARK7 protects against septic AKI through suppressing NF-κB signaling [4]. In CD4+ regulatory T cells (Treg cells), Park7 (Dj-1) deletion impairs Treg survival in young mice and reduces Treg homeostatic proliferation and cellularity in aged mice, leading to increased severity in aged mice during the remission of experimental autoimmune encephalomyelitis (EAE) [3].

In conclusion, PARK7 plays essential roles in multiple biological processes. Its deficiency in KO mouse models reveals its significance in diseases such as Parkinson's disease, endotoxic acute kidney injury, and autoimmune diseases like EAE. These findings highlight PARK7 as a potential therapeutic target for these diseases.

References:

1. Skou, Line Duborg, Johansen, Steffi Krudt, Okarmus, Justyna, Meyer, Morten. 2024. Pathogenesis of DJ-1/PARK7-Mediated Parkinson's Disease. In Cells, 13, . doi:10.3390/cells13040296. https://pubmed.ncbi.nlm.nih.gov/38391909/

2. Pap, Domonkos, Veres-Székely, Apor, Szebeni, Beáta, Vannay, Ádám. 2022. PARK7/DJ-1 as a Therapeutic Target in Gut-Brain Axis Diseases. In International journal of molecular sciences, 23, . doi:10.3390/ijms23126626. https://pubmed.ncbi.nlm.nih.gov/35743072/

3. Danileviciute, Egle, Zeng, Ni, Capelle, Christophe M, Ollert, Markus, Hefeng, Feng Q. 2022. PARK7/DJ-1 promotes pyruvate dehydrogenase activity and maintains Treg homeostasis during ageing. In Nature metabolism, 4, 589-607. doi:10.1038/s42255-022-00576-y. https://pubmed.ncbi.nlm.nih.gov/35618940/

4. Li, Honglin, Liu, Zhiwen, Wang, Ying, Tang, Chengyuan, Dong, Zheng. . PARK7 is induced to protect against endotoxic acute kidney injury by suppressing NF-κB. In Clinical science (London, England : 1979), 136, 1877-1891. doi:10.1042/CS20220493. https://pubmed.ncbi.nlm.nih.gov/36449316/