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Genetic disruption of zebrafish mab21l1 reveals a conserved role in eye development and affected pathways. Dev Dyn 2021 Aug;250(8):1056-1073

Date

02/12/2021

Pubmed ID

33570754

Pubmed Central ID

PMC8349561

DOI

10.1002/dvdy.312

Scopus ID

2-s2.0-85102653887 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

BACKGROUND: The male-abnormal 21 like (MAB21L) genes are important in human ocular development. Homozygous loss of MAB21L1 leads to corneal dystrophy in all affected individuals along with cataracts and buphthalmos in some. The molecular function and downstream pathways of MAB21L factors are largely undefined.

RESULTS: We generated the first mab21l1 zebrafish mutant carrying a putative loss-of-function allele, c.107delA p.(Lys36Argfs*7). At the final stages of embryonic development, homozygous mab21l1c.107delA fish displayed enlarged anterior chambers and corneal thinning which progressed with age. Additional studies revealed increased cell death in the mutant corneas, transformation of the cornea into a skin-like epithelium, and progressive lens degeneration with development of fibrous masses in the anterior chamber. RNA-seq of wild-type and mutant ocular transcriptomes revealed significant changes in expression of several genes, including irf1a and b, stat1, elf3, krt17, tlr9, and loxa associated with immunity and/or corneal function. Abnormal expression of lysyl oxidases have been previously linked with corneal thinning, fibrosis, and lens defects in mammals, suggesting a role for loxa misexpression in the progressive mab21l1c.107delA eye phenotype.

CONCLUSIONS: Zebrafish mab21l1 is essential for normal corneal development, similar to human MAB21L1. The identified molecular changes in mab21l1c.107delA mutants provide the first clues about possible affected pathways.

Author List

Seese SE, Deml B, Muheisen S, Sorokina E, Semina EV

Author

Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Animals, Genetically Modified
Cornea
Embryonic Development
Eye
Homeodomain Proteins
Lens, Crystalline
Organogenesis
Phenotype
Zebrafish
Zebrafish Proteins