Sftpd-KO Mouse

Sftpd, encoding surfactant protein D, is a lung-specific protein and a pattern recognition molecule belonging to the collectin family [3,4]. It is involved in surfactant metabolism [1], and plays key regulatory roles in maintaining overall lung function, likely through its anti-inflammatory and immunomodulatory properties [4,5].

In a study on lung-metastatic colorectal cancer, Sftpd was identified as a hub gene, and it was found to facilitate cellular proliferation and lung metastasis in CRC, suggesting its potential as a therapeutic target in this disease [1]. In gene-targeted mouse models, the deletion of Sftpd, along with Sftpa1, was initially thought to cause retinal degeneration, but this was later disproven due to an unrecognized Pde6brd1 genotype from earlier breeding. After outbreeding this mutation, normal retinal histology was restored, indicating that loss of Sftpd does not directly result in retinal degeneration [2].

In summary, Sftpd is crucial for lung function, especially in surfactant-related processes. Although its role in retinal degeneration was refuted in gene-targeted mouse models, its significance in cancer, such as its role in promoting lung metastasis in colorectal cancer, highlights its importance in understanding disease mechanisms and developing potential therapies for certain malignancies [1,2].

References:

1. Dai, Wei, Guo, Caiyao, Wang, Yu, Wang, Yun, Liu, Shenglan. 2023. Identification of hub genes and pathways in lung metastatic colorectal cancer. In BMC cancer, 23, 323. doi:10.1186/s12885-023-10792-8. https://pubmed.ncbi.nlm.nih.gov/37024866/

2. Bhatti, Faizah, Kung, Johannes W, Vieira, Frederico. 2018. Retinal degeneration mutation in Sftpa1tm1Kor/J and Sftpd -/- targeted mice. In PloS one, 13, e0199824. doi:10.1371/journal.pone.0199824. https://pubmed.ncbi.nlm.nih.gov/29969487/

3. Hoffmann-Petersen, Benjamin, Suffolk, Raymond, Petersen, Jens J H, Sorensen, Grith L, Agertoft, Lone. 2021. Association of serum surfactant protein D and SFTPD gene variants with asthma in Danish children, adolescents, and young adults. In Immunity, inflammation and disease, 10, 189-200. doi:10.1002/iid3.560. https://pubmed.ncbi.nlm.nih.gov/34780682/

4. Nandy, Debparna, Sharma, Nidhi, Senapati, Sabyasachi. 2019. Systematic Review and Meta-Analysis Confirms Significant Contribution of Surfactant Protein D in Chronic Obstructive Pulmonary Disease. In Frontiers in genetics, 10, 339. doi:10.3389/fgene.2019.00339. https://pubmed.ncbi.nlm.nih.gov/31057601/

5. Sorensen, Grith L, Bladbjerg, Else Marie, Steffensen, Rudi, Drivsholm, Thomas, Holmskov, Uffe. 2015. Association between the surfactant protein D (SFTPD) gene and subclinical carotid artery atherosclerosis. In Atherosclerosis, 246, 7-12. doi:10.1016/j.atherosclerosis.2015.12.037. https://pubmed.ncbi.nlm.nih.gov/26748346/