Jade1, also known as PHF17, is a candidate transcription co-factor essential for DNA replication, cell division, and cell cycle regulation. It is involved in the WNT signaling pathway, where it promotes β-catenin ubiquitination and blunts canonical WNT signaling [1,4]. The protein is also part of the HBO histone acetyltransferase complex, with potential implications in gene transcription regulation [3]. Genetic models, such as knockout mouse lines, are valuable tools for studying its function.

A Jade1 knockout mouse line generated using CRISPR-Cas9 technology showed that Jade1 null resulted in decreased survival rate, reduced body weight and brain weight, yet histological analysis revealed normal brain development. RNA-seq analysis further indicated that Jade1 loss did not affect cerebral cortex gene expression, suggesting Jade1 is dispensable for developing the cerebral cortex in mice [1]. In a genome-wide association study, JADE1 was associated with tauopathy. Knockdown of the Drosophila JADE1 homolog enhanced tau-induced toxicity and apoptosis in vivo in a humanized tau knock-in model, suggesting a role for JADE1 as a modifier of neurofibrillary degeneration [2].

In conclusion, Jade1 plays diverse roles in biological processes including cell cycle regulation and potentially in disease-related pathways such as tauopathy. The use of knockout mouse models has been crucial in uncovering its dispensability in cerebral cortex development and its association with tauopathy, contributing to our understanding of the underlying biological mechanisms and disease-related functions of Jade1.

References:

1. Wang, Jingpeng, Chai, Baihui, Yang, Yanlang, Wang, Zhao-Qi, Li, Tangliang. 2023. JADE1 is dispensable for the brain development in mice. In Biochemical and biophysical research communications, 695, 149421. doi:10.1016/j.bbrc.2023.149421. https://pubmed.ncbi.nlm.nih.gov/38171233/

2. Farrell, Kurt, Kim, SoongHo, Han, Natalia, White Iii, Charles L, Crary, John F. 2021. Genome-wide association study and functional validation implicates JADE1 in tauopathy. In Acta neuropathologica, 143, 33-53. doi:10.1007/s00401-021-02379-z. https://pubmed.ncbi.nlm.nih.gov/34719765/

3. Wu, Yifan, Manna, Asit K, Li, Li, Chandrasekharan, Mahesh B, Tantin, Dean. 2025. Jade1 and the HBO1 complex are spatial-selective cofactors of Oct4. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.11.07.622531. https://pubmed.ncbi.nlm.nih.gov/39574712/

4. Shafique, Shagufta, Rashid, Sajid. 2018. Structural basis for renal cancer by the dynamics of pVHL-dependent JADE1 stabilization and β-catenin regulation. In Progress in biophysics and molecular biology, 145, 65-77. doi:10.1016/j.pbiomolbio.2018.12.005. https://pubmed.ncbi.nlm.nih.gov/30528740/