PUBLICATION
Genetic disruption of zebrafish mab21l1 reveals a conserved role in eye development and affected pathways
- Authors
- Seese, S.E., Deml, B., Muheisen, S., Sorokina, E., Semina, E.V.
- ID
- ZDB-PUB-210212-8
- Date
- 2021
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 250(8): 1056-1073 (Journal)
- Registered Authors
- Semina, Elena
- Keywords
- IRF1, LOX, MAB21L1, TALEN, cataracts, corneal dystrophy, transcriptome
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cornea/embryology
- Cornea/metabolism
- Embryonic Development/genetics
- Eye/embryology*
- Eye/metabolism
- Homeodomain Proteins/genetics*
- Homeodomain Proteins/metabolism
- Lens, Crystalline/embryology
- Lens, Crystalline/metabolism
- Organogenesis/genetics*
- Phenotype
- Zebrafish
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 33570754 Full text @ Dev. Dyn.
Citation
Seese, S.E., Deml, B., Muheisen, S., Sorokina, E., Semina, E.V. (2021) Genetic disruption of zebrafish mab21l1 reveals a conserved role in eye development and affected pathways. Developmental Dynamics : an official publication of the American Association of Anatomists. 250(8):1056-1073.
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. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping