Adam21, a member of the disintegrin and metalloprotease (ADAM) family of transmembrane proteins, has been implicated in multiple biological processes. ADAMs are involved in diverse functions such as cleaving cell-surface proteins, cell adhesion, and intracellular signaling [2]. Adam21 may play a role in neural regenerative processes upon neuronal injury, and is also potentially associated with cell motility and metastasis [2,3].

Using the CRISPR/Cas9 system, Adam21-null mice were generated to explore its role in male reproduction. The study found that male mice lacking Adam21 had normal fertility, with no detectable defects in spermatogenesis, sperm motility, meiotic progression, or Sertoli and Leydig cells. This suggests that Adam21 might not be essential for male fertility in mice [1].

In hepatocellular carcinoma, knockdown of ADAM21 in the KYN-2 cell line reduced invasion, migration, proliferation, and metastasis. In clinical specimens, ADAM21 positivity was associated with vascular invasion, large tumor size, high histological grade, and lower survival rates, indicating its role in HCC metastasis and its potential as a prognostic marker [3].

In conclusion, while Adam21 does not seem to be essential for male fertility in mice, it may play a role in cancer metastasis, especially in hepatocellular carcinoma. The use of Adam21-null mouse models has provided insights into its non-essential role in male reproductive processes, and further research could potentially uncover more about its functions in disease-related cell motility and metastasis [1,3].

References:

1. Chen, Yinghong, Liu, Chao, Shang, Yongliang, Li, Wei, Li, Guoping. 2021. Adam21 is dispensable for reproductive processes in mice. In PeerJ, 9, e12210. doi:10.7717/peerj.12210. https://pubmed.ncbi.nlm.nih.gov/34631320/

2. Hsia, Hung-En, Tüshaus, Johanna, Brummer, Tobias, Scilabra, Simone D, Lichtenthaler, Stefan F. 2019. Functions of 'A disintegrin and metalloproteases (ADAMs)' in the mammalian nervous system. In Cellular and molecular life sciences : CMLS, 76, 3055-3081. doi:10.1007/s00018-019-03173-7. https://pubmed.ncbi.nlm.nih.gov/31236626/

3. Honda, Hiroki, Takamura, Masaaki, Yamagiwa, Satoshi, Aoyagi, Yutaka, Terai, Shuji. 2017. Overexpression of a disintegrin and metalloproteinase 21 is associated with motility, metastasis, and poor prognosis in hepatocellular carcinoma. In Scientific reports, 7, 15485. doi:10.1038/s41598-017-15800-z. https://pubmed.ncbi.nlm.nih.gov/29138461/