Abstract:
Background Microphthalmia, 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 malforma‑
tions is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular devel‑
opmental 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. Addi‑
tionally, 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.
Results Query of the International Mouse Phenotyping Consortium (IMPC) database (data release 17.0, August 01,
2022) identifed 74 unique knockout lines (genes) with genetically associated eye defects in mouse embryos. The vast
majority of eye abnormalities were small or absent eyes, fndings 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 identifed in the original publications. These 12 previously published gene knockouts with no
reported ocular abnormalities and the 47 unpublished knockouts with ocular abnormalities identifed by the IMPC
represent 59 genes not previously associated with early eye development in mice. Of these 59, we identifed 19 genes