PUBLICATION
Variable phenotypes and penetrance between and within different zebrafish ciliary transition zone mutants
- Authors
- Wang, J., Thomas, H.R., Thompson, R.G., Waldrep, S.C., Fogerty, J., Song, P., Li, Z., Ma, Y., Santra, P., Hoover, J.D., Yeo, N.C., Drummond, I.A., Yoder, B.K., Amack, J.D., Perkins, B., Parant, J.M.
- ID
- ZDB-PUB-221220-6
- Date
- 2022
- Source
- Disease models & mechanisms 15(12): (Journal)
- Registered Authors
- Keywords
- CRISPR, Cilia, Crispant, Joubert syndrome, Meckel syndrome, Nephronophthisis, Penetrance, Pronephric cysts, Retinal degeneration, Scoliosis, Transition zone, Zebrafish
- Datasets
- GEO:GSE217001
- MeSH Terms
-
- Animals
- Biological Variation, Population
- Cilia*/metabolism
- Penetrance
- Polycystic Kidney Diseases*/metabolism
- Syndrome
- Vesicular Transport Proteins/genetics
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 36533556 Full text @ Dis. Model. Mech.
Citation
Wang, J., Thomas, H.R., Thompson, R.G., Waldrep, S.C., Fogerty, J., Song, P., Li, Z., Ma, Y., Santra, P., Hoover, J.D., Yeo, N.C., Drummond, I.A., Yoder, B.K., Amack, J.D., Perkins, B., Parant, J.M. (2022) Variable phenotypes and penetrance between and within different zebrafish ciliary transition zone mutants. Disease models & mechanisms. 15(12):.
Abstract
Meckel syndrome, nephronophthisis, Joubert syndrome and Bardet-Biedl syndrome are caused by mutations in proteins that localize to the ciliary transition zone (TZ). The phenotypically distinct syndromes suggest that these TZ proteins have differing functions. However, mutations in a single TZ gene can result in multiple syndromes, suggesting that the phenotype is influenced by modifier genes. We performed a comprehensive analysis of ten zebrafish TZ mutants, including mks1, tmem216, tmem67, rpgrip1l, cc2d2a, b9d2, cep290, tctn1, nphp1 and nphp4, as well as mutants in ift88 and ift172. Our data indicate that variations in phenotypes exist between different TZ mutants, supporting different tissue-specific functions of these TZ genes. Further, we observed phenotypic variations within progeny of a single TZ mutant, reminiscent of multiple disease syndromes being associated with mutations in one gene. In some mutants, the dynamics of the phenotype became complex with transitory phenotypes that are corrected over time. We also demonstrated that multiple-guide-derived CRISPR/Cas9 F0 'crispant' embryos recapitulate zygotic null phenotypes, and rapidly identified ciliary phenotypes in 11 cilia-associated gene candidates (ankfn1, ccdc65, cfap57, fhad1, nme7, pacrg, saxo2, c1orf194, ttc26, zmynd12 and cfap52).
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping