Genome-wide screening reveals the genetic basis of mammalian embryonic eye development

0570766 - ÚMG 2024 RIV GB eng J - Článek v odborném periodiku
Chee, J. - Lanoue, L. - Clary, D. L. - Higgins, K. - Bower, L. - Flenniken, A. - Guo, R. - Adams, D. - Bosch, F. - Braun, R. E. - Brown, S. D. M. - Chin, H. J. G. - Dickinson, M. - Hsu, C. - Dobbie, M. - Gao, X. - Galande, S. - Grobler, A. - Heaney, J. - Herault, Y. - de Angelis, M. H. - Mammano, F. - Nutter, Lauryl M. J. - Parkinson, H. - Qin, C. - Shiroishi, T. - Sedláček, Radislav - Seong, J. - Xu, Y. - Brooks, B. … celkem 35 autorů
Genome-wide screening reveals the genetic basis of mammalian embryonic eye development.
BMC BIOLOGY. Roč. 21, č. 1 (2023), č. článku 22. E-ISSN 1741-7007
Institucionální podpora: RVO:68378050
Klíčová slova: MAC spectrum * Eye development * Mouse * impc * Serine-glycine biosynthesis * cplane
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 5.4, rok: 2022
Způsob publikování: Open access
https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01475-0

BackgroundMicrophthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways required for early eye development through systematic forward screening of the mammalian genome.ResultsQuery of the International Mouse Phenotyping Consortium (IMPC) database (data release 17.0, August 01, 2022) identified 74 unique knockout lines (genes) with genetically associated eye defects in mouse embryos. The vast majority of eye abnormalities were small or absent eyes, findings most relevant to MAC spectrum disease in humans. A literature search showed that 27 of the 74 lines had previously published knockout mouse models, of which only 15 had ocular defects identified in the original publications. These 12 previously published gene knockouts with no reported ocular abnormalities and the 47 unpublished knockouts with ocular abnormalities identified by the IMPC represent 59 genes not previously associated with early eye development in mice. Of these 59, we identified 19 genes with a reported human eye phenotype. Overall, mining of the IMPC data yielded 40 previously unimplicated genes linked to mammalian eye development. Bioinformatic analysis showed that several of the IMPC genes colocalized to several protein anabolic and pluripotency pathways in early eye development. Of note, our analysis suggests that the serine-glycine pathway producing glycine, a mitochondrial one-carbon donator to folate one-carbon metabolism (FOCM), is essential for eye formation.ConclusionsUsing genome-wide phenotype screening of single-gene knockout mouse lines, STRING analysis, and bioinformatic methods, this study identified genes heretofore unassociated with MAC phenotypes providing models to research novel molecular and cellular mechanisms involved in eye development. These findings have the potential to hasten the diagnosis and treatment of this congenital blinding disease.
Trvalý link: https://hdl.handle.net/11104/0348990