Dnajb3, also known as a DNAJ (Heat shock protein 40; Hsp40) homolog, subfamily B, member 3 chaperone protein, plays a crucial role in metabolic regulation. It is involved in pathways related to insulin signaling and glucose homeostasis, and is associated with metabolic stress responses [1,3,4]. The study of Dnajb3 using genetic models like gene knockout mouse models can provide insights into its in-vivo functions.

In a study generating three Dnajb3 knockout (KO) lines (KO 30, 44 and 47) with CRISPR-Cas9, male and female KO 47 mice fed a high-fat (HF) diet showed higher body weight and fat mass compared to wild-type littermates. They also had slower glucose clearance in glucose tolerance tests, consistent with decreased GLUT4 gene mRNA expression in white adipose tissue. Additionally, male KO 47 mice had increased mRNA levels of pro-inflammatory and ER stress markers. These phenotypes suggest Dnajb3 may be important in metabolic functions and glucose homeostasis [2].

In conclusion, Dnajb3 is essential for maintaining metabolic functions and glucose homeostasis. The Dnajb3 KO mouse models have revealed its role in obesity-induced metabolic changes, highlighting its potential as a therapeutic target for obesity and type 2 diabetes [2].

References:

1. Islam, Zeyaul, Diane, Abdoulaye, Khattab, Namat, Thornalley, Paul, Kolatkar, Prasanna R. 2023. DNAJB3 attenuates ER stress through direct interaction with AKT. In PloS one, 18, e0290340. doi:10.1371/journal.pone.0290340. https://pubmed.ncbi.nlm.nih.gov/37594932/

2. Nejat, Shadi, Menikdiwela, Kalhara R, Efotte, Aliyah, Dehbi, Mohammed, Moustaid-Moussa, Naima. 2023. Genetic Deletion of DNAJB3 Using CRISPR-Cas9, Produced Discordant Phenotypes. In Genes, 14, . doi:10.3390/genes14101857. https://pubmed.ncbi.nlm.nih.gov/37895206/

3. Arredouani, Abdelilah, Diane, Abdoulaye, Khattab, Namat, Abou-Samra, Abdul Badi, Dehbi, Mohammed. 2019. DNAJB3 attenuates metabolic stress and promotes glucose uptake by eliciting Glut4 translocation. In Scientific reports, 9, 4772. doi:10.1038/s41598-019-41244-8. https://pubmed.ncbi.nlm.nih.gov/30886231/

4. Abu-Farha, Mohamed, Cherian, Preethi, Al-Khairi, Irina, Behbehani, Kazem, Abubaker, Jehad. 2015. DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression. In Scientific reports, 5, 14448. doi:10.1038/srep14448. https://pubmed.ncbi.nlm.nih.gov/26400768/