June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Temporal and spatial inhibition of Mab21L2 as a model system for coloboma and anophhtalmia
Author Affiliations & Notes
  • Lena Gunhaga
    Umeå Centre for Molecular Medicine, Umea, Sweden
  • Footnotes
    Commercial Relationships   Lena Gunhaga, None
  • Footnotes
    Support  KMA Foundation, Swedish Eye Foundation
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 115. doi:
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      Lena Gunhaga; Temporal and spatial inhibition of Mab21L2 as a model system for coloboma and anophhtalmia. Invest. Ophthalmol. Vis. Sci. 2017;58(8):115.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : During development Mab21L2 has been shown to be expressed in eye, midbrain, branchial arches and forelimb. Different missense mutations in Mab21L2 have been identified in unrelated families with various bilateral eye malformations, such as coloboma, microphthalmia and anophthalmia, and often associated with intellectual disability and skeletal dysplasia. Mouse Mab21L2 knockout embryos exhibit rudimentary retina and aphakia due to improper invagination of the optic vesicle, and die around embryonic day (E) 13.5 because of disrupted heart formation. Since the temporal requirement of Mab21L2 cannot be studied in knockout mice, there is a need to develop other Mab21L2 eye disease model systems. This would allow for molecular studies concerning Mab21L2 downstream mechanisms.

Methods : To inhibit Mab21L2 activity, we have in ovo electroporated long double strand Mab21L2-RNA in the prospective optic region in chick embryos at early stages, and incubated the embryos to a range of stages. The morphology of the viable embryos has been analyzed in relation to molecular markers using in situ hybridization and immunohistochemistry.

Results : Our preliminary results show that inhibition of Mab21L2 around neural fold stages (stage 8-9) results in anophthalmia (Fig). In contrast, inhibition of Mab21L2 at early optic cup stages (stage 10-11) results in coloboma (referred as coloboma eyes) (Fig). 24 hours after inhibition of Mab21L2, coloboma eyes exhibit a decrease in cell proliferation, whereas cell death appears to be unaffected. Moreover, the basal accumulation of F-actin, important for cytoskeletal rearrangement, is disrupted. 48 hours after inhibition of Mab21L2, our preliminary data indicate a decrease in Pax6+ proliferative retinal cells. Together this might explain the improper invagination of the optic vesicle observed in Mab21L2-/- mice. In E6 coloboma eyes, our preliminary data suggest a delay or disruption of the differentiation of retinal ganglion cells. In relation to this, the development of the optic nerve head is disrupted, and the neurofilament marker NFM was severely reduced or completely absent in this region.

Conclusions : We have developed a chick model system to analyze downstream effects of Mab21L2 inhibition in a temporal manner, and conclude that early inhibition of Mab21L2 leads to anophthalmia, and slightly later blockage generate coloboma formation.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.


Mab21L2 inhibition by dsRNA electroporation

Mab21L2 inhibition by dsRNA electroporation


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