AI Article Synopsis
- The study focuses on the role of the MAB21L genes in eye development, specifically the effects of the loss of the MAB21L1 gene, which leads to eye conditions like corneal dystrophy and cataracts.
- Researchers created a zebrafish model with a mutation in the mab21l1 gene, observing abnormal eye development characterized by enlarged chambers, corneal thinning, and cell death in the corneas.
- RNA sequencing revealed significant changes in gene expression related to immune response and corneal function, suggesting that MAB21L1 is crucial for normal eye development and may involve specific pathways that remain largely unexplored.
Article 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 mab21l1 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 mab21l1 eye phenotype.
Conclusions: Zebrafish mab21l1 is essential for normal corneal development, similar to human MAB21L1. The identified molecular changes in mab21l1 mutants provide the first clues about possible affected pathways.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349561 | PMC |
| http://dx.doi.org/10.1002/dvdy.312 | DOI Listing |
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