Dnajb7-KO Mouse

DnaJ heat shock protein family (Hsp40) member B7, also known as DNAJB7, is a member of the highly conserved DNAJBs proteins. These proteins are involved in various biological processes, and DNAJB7 in particular has been linked to protein translation [3]. It may also be involved in pathways related to chaperone-mediated protein folding and endoplasmic reticulum proteostasis, as its decreased expression was noted in classical Ehlers-Danlos syndrome patients' skin fibroblasts, where genes related to these functions were affected [4].

To study its role in male reproduction, Dnajb7-deficient mice were generated using the CRISPR/Cas9-mediated genome editing system. The results showed that DNAJB7 is specifically expressed in haploid germ cells, but Dnajb7 knockout mice are fertile with no detectable defects in Sertoli cells, spermatogonia, meiotic and postmeiotic cells. This indicates that DNAJB7 is not essential for spermatogenesis and is dispensable for male fertility in mice [1]. In addition, DNAJB7 was identified as a novel cancer-testis antigen. It is expressed in many tumors and is strongly immunogenic in cancer patients. DNAJB7-specific T cells can kill colorectal tumor lines in vitro, and the IFNγ+ response can be enhanced by cyclophosphamide-mediated immunosuppression control [2]. Also, in a study on the effect of a Chinese 2-herb formula on endothelial cells, DNAJB7 was found to be involved in the wound healing angiogenesis process, specifically in protein translation [3].

In conclusion, DNAJB7's role in protein translation and potentially in chaperone-related functions is significant. The Dnajb7 knockout mouse model has been crucial in demonstrating its non-essential role in spermatogenesis and male fertility. Its identification as a cancer-testis antigen and its involvement in wound healing angiogenesis also highlight its importance in cancer immunotherapy and wound-related research areas.

References:

1. Bai, Shun, Hu, Meihong, Yu, Lina, Tong, Xianhong, Yue, Qiuling. 2023. DNAJB7 is dispensable for male fertility in mice. In Reproductive biology and endocrinology : RB&E, 21, 32. doi:10.1186/s12958-023-01086-6. https://pubmed.ncbi.nlm.nih.gov/37004113/

2. Scurr, Martin J, Greenshields-Watson, Alex, Campbell, Emma, Gallimore, Awen, Godkin, Andrew. 2020. Cancer Antigen Discovery Is Enabled by RNA Sequencing of Highly Purified Malignant and Nonmalignant Cells. In Clinical cancer research : an official journal of the American Association for Cancer Research, 26, 3360-3370. doi:10.1158/1078-0432.CCR-19-3087. https://pubmed.ncbi.nlm.nih.gov/32122920/

3. Tam, Jacqueline Chor Wing, Ko, Chun Hay, Koon, Chi Man, Chan, Wai Yee, Lau, Clara Bik San. 2015. Identification of Target Genes Involved in Wound Healing Angiogenesis of Endothelial Cells with the Treatment of a Chinese 2-Herb Formula. In PloS one, 10, e0139342. doi:10.1371/journal.pone.0139342. https://pubmed.ncbi.nlm.nih.gov/26430762/

4. Chiarelli, Nicola, Carini, Giulia, Zoppi, Nicoletta, Ritelli, Marco, Colombi, Marina. 2019. Molecular insights in the pathogenesis of classical Ehlers-Danlos syndrome from transcriptome-wide expression profiling of patients' skin fibroblasts. In PloS one, 14, e0211647. doi:10.1371/journal.pone.0211647. https://pubmed.ncbi.nlm.nih.gov/30716086/