Bend2-KO Mouse

BEND2, short for BEN domain containing 2, has been identified as a key regulator in mouse spermatogenesis. It is specifically expressed in spermatogenic cells around meiotic initiation and plays an essential role in meiotic progression. Bend2 knockout in male mice arrests meiosis at the transition from zygonema to pachynema, disrupts synapsis and DNA double-strand break repair, and induces non-homologous chromosomal pairing. BEND2 also interacts with chromatin-associated proteins in transcription-repressor complexes, inhibits genes involved in meiotic initiation, and regulates chromatin accessibility and H3K4me3 modification [3].

In addition, BEND2 is frequently involved in gene fusions associated with various tumors. For example, the MN1-BEND2 fusion is characteristic of early ependymal tumor (EET), which mostly affects female children and has a good prognosis after surgical management [1]. EWSR1-BEND2 fusion defines an epigenetically distinct subtype of astroblastoma, and spinal cord astroblastomas with this fusion have been reported, often showing aggressive recurrence [2,4]. A soft-tissue sarcoma with MN1-BEND2 fusion was also described, highlighting the pleiotropic nature of this fusion gene [5]. There are also reports of a malignant bone-forming neoplasm with NIPBL::BEND2 fusion, a paediatric astroblastoma-like neuroepithelial tumour of the spinal cord with a MAMLD1-BEND2 rearrangement, and a malignant salivary gland neoplasm of the tongue base with EWSR1::BEND2 fusion [6,7,9]. Whole-genome sequencing has also suggested BEND2 may be involved in spermatogenesis in relation to non-obstructive azoospermia [8].

In conclusion, BEND2 is crucial for meiotic progression during mouse spermatogenesis. Its involvement in gene fusions in multiple tumor types indicates its potential significance in tumorigenesis. Studies using gene knockout models in mice have been instrumental in uncovering its role in meiosis, and further research may shed more light on its role in the context of various diseases, especially tumors.

References:

1. Lehman, Norman L. 2023. Early ependymal tumor with MN1-BEND2 fusion: a mostly cerebral tumor of female children with a good prognosis that is distinct from classical astroblastoma. In Journal of neuro-oncology, 161, 425-439. doi:10.1007/s11060-022-04222-1. https://pubmed.ncbi.nlm.nih.gov/36604386/

2. Lucas, Calixto-Hope G, Gupta, Rohit, Wu, Jasper, Berger, Mitchel S, Solomon, David A. 2021. EWSR1-BEND2 fusion defines an epigenetically distinct subtype of astroblastoma. In Acta neuropathologica, 143, 109-113. doi:10.1007/s00401-021-02388-y. https://pubmed.ncbi.nlm.nih.gov/34825267/

3. Ma, Longfei, Xie, Dan, Luo, Mengcheng, Duo, Shuguang, Han, Chunsheng. 2022. Identification and characterization of BEND2 as a key regulator of meiosis during mouse spermatogenesis. In Science advances, 8, eabn1606. doi:10.1126/sciadv.abn1606. https://pubmed.ncbi.nlm.nih.gov/35613276/

4. Fu, Lingyi, Lao, I Weng, Huang, Liyun, Hu, Wanming, Xi, Shaoyan. 2024. Spinal Cord Astroblastoma With EWSR1-BEND2 Fusion in Female Patients : A Report of Four Cases From China and a Comprehensive Literature Review. In The American journal of surgical pathology, 48, 1372-1380. doi:10.1097/PAS.0000000000002298. https://pubmed.ncbi.nlm.nih.gov/39104157/

5. Yoshida, Akihiko, Satomi, Kaishi, Kobayashi, Eisuke, Kawai, Akira, Mori, Taisuke. 2022. Soft-tissue sarcoma with MN1-BEND2 fusion: A case report and comparison with astroblastoma. In Genes, chromosomes & cancer, 61, 427-431. doi:10.1002/gcc.23028. https://pubmed.ncbi.nlm.nih.gov/35094441/

6. Dashti, Nooshin K, Matcuk, George, Agaimy, Abbas, Saoud, Carla, Antonescu, Cristina R. . Malignant Bone-Forming Neoplasm With NIPBL::BEND2 Fusion. In Genes, chromosomes & cancer, 63, e70015. doi:10.1002/gcc.70015. https://pubmed.ncbi.nlm.nih.gov/39604143/

7. Rossi, Sabrina, Barresi, Sabina, Colafati, Giovanna Stefania, Gessi, Marco, Alaggio, Rita. 2022. Paediatric astroblastoma-like neuroepithelial tumour of the spinal cord with a MAMLD1-BEND2 rearrangement. In Neuropathology and applied neurobiology, 48, e12814. doi:10.1111/nan.12814. https://pubmed.ncbi.nlm.nih.gov/35301744/

8. Malcher, Agnieszka, Stokowy, Tomasz, Berman, Andrea, Yatsenko, Alexander N, Kurpisz, Maciej K. 2022. Whole-genome sequencing identifies new candidate genes for nonobstructive azoospermia. In Andrology, 10, 1605-1624. doi:10.1111/andr.13269. https://pubmed.ncbi.nlm.nih.gov/36017582/

9. Zhang, Yuan-Dong, Sun, Jiang-Jie, Xi, Shao-Yan, Yang, Qiong, Zhang, Xu-Chao. 2024. Malignant Salivary Gland Neoplasm of the Tongue Base with EWSR1::BEND2 Fusion: An Unusual Case with Literature Review. In Head and neck pathology, 18, 118. doi:10.1007/s12105-024-01726-2. https://pubmed.ncbi.nlm.nih.gov/39495374/