Cfap74-KO Mouse

Cfap74, also known as Cilia and Flagella Associated Protein 74, is involved in the proper functioning of cilia and flagella, playing a significant role in processes like mucociliary clearance and sperm motility. It is associated with pathways related to ciliary function, and its disruption can lead to various disorders [3].

Mutations in Cfap74 have been found to cause primary ciliary dyskinesia (PCD) with normal ciliary ultrastructure [1]. Pathogenic variants in Cfap74 also result in PCD with a defective C1d projection of the ciliary central apparatus, which is associated with normal situs, nasal nitric oxide production, ciliary ultrastructure, and ciliary beating, but still leads to chronic respiratory disease due to insufficient ciliary clearance [2]. Biallelic mutations in Cfap74 may cause human PCD and the multiple morphological abnormalities of the sperm flagella (MMAF) phenotype, highlighting its importance in these disorders [3]. In zebrafish models, knockdown of cfap74 led to abnormalities in cardiac looping and expression patterns of early signaling molecules, as well as impairments in Kupffer's vesicle organogenesis or ciliogenesis, suggesting its role in the establishment of laterality patterns [4].

In conclusion, Cfap74 is essential for the normal function of cilia and flagella, with its disruption leading to PCD and MMAF. The use of genetic models like zebrafish has provided insights into its role in laterality establishment. Understanding Cfap74's function contributes to the genetic diagnosis of related disorders and may help predict pregnancy outcomes in in vitro fertilization.

References:

1. Biebach, Luisa, Cindrić, Sandra, Koenig, Julia, Olbrich, Heike, Omran, Heymut. . Recessive Mutations in CFAP74 Cause Primary Ciliary Dyskinesia with Normal Ciliary Ultrastructure. In American journal of respiratory cell and molecular biology, 67, 409-413. doi:10.1165/rcmb.2022-0032LE. https://pubmed.ncbi.nlm.nih.gov/36047773/

2. Wohlgemuth, Kai, Hoersting, Niklas, Koenig, Julia, Dworniczak, Bernd, Omran, Heymut. 2024. Pathogenic variants in CFAP46, CFAP54, CFAP74 and CFAP221 cause primary ciliary dyskinesia with a defective C1d projection of the central apparatus. In The European respiratory journal, 64, . doi:10.1183/13993003.00790-2024. https://pubmed.ncbi.nlm.nih.gov/39362668/

3. Sha, Yanwei, Wei, Xiaoli, Ding, Lu, Zhang, Xuequan, Lin, Shaobin. 2020. Biallelic mutations of CFAP74 may cause human primary ciliary dyskinesia and MMAF phenotype. In Journal of human genetics, 65, 961-969. doi:10.1038/s10038-020-0790-2. https://pubmed.ncbi.nlm.nih.gov/32555313/

4. Liu, Sijie, Wei, Wei, Wang, Pengcheng, Sun, Kun, Xu, Rang. 2022. LOF variants identifying candidate genes of laterality defects patients with congenital heart disease. In PLoS genetics, 18, e1010530. doi:10.1371/journal.pgen.1010530. https://pubmed.ncbi.nlm.nih.gov/36459505/