PMID- 33570754
OWN - NLM
STAT- MEDLINE
DCOM- 20220329
LR  - 20240301
IS  - 1097-0177 (Electronic)
IS  - 1058-8388 (Print)
IS  - 1058-8388 (Linking)
VI  - 250
IP  - 8
DP  - 2021 Aug
TI  - Genetic disruption of zebrafish mab21l1 reveals a conserved role in eye 
      development and affected pathways.
PG  - 1056-1073
LID - 10.1002/dvdy.312 [doi]
AB  - 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(c.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 
      mab21l1(c.107delA) eye phenotype. CONCLUSIONS: Zebrafish mab21l1 is essential for 
      normal corneal development, similar to human MAB21L1. The identified molecular 
      changes in mab21l1(c.107delA) mutants provide the first clues about possible 
      affected pathways.
CI  - (c) 2021 American Association of Anatomists.
FAU - Seese, Sarah E
AU  - Seese SE
AD  - Department of Pediatrics, The Medical College of Wisconsin, Milwaukee, Wisconsin, 
      USA.
AD  - Cell Biology, Neurobiology and Anatomy, The Medical College of Wisconsin, 
      Milwaukee, Wisconsin, USA.
FAU - Deml, Brett
AU  - Deml B
AD  - Department of Pediatrics, The Medical College of Wisconsin, Milwaukee, Wisconsin, 
      USA.
AD  - Cell Biology, Neurobiology and Anatomy, The Medical College of Wisconsin, 
      Milwaukee, Wisconsin, USA.
AD  - PreventionGenetics, Marshfield, Wisconsin, USA.
FAU - Muheisen, Sanaa
AU  - Muheisen S
AD  - Department of Pediatrics, The Medical College of Wisconsin, Milwaukee, Wisconsin, 
      USA.
FAU - Sorokina, Elena
AU  - Sorokina E
AD  - Department of Pediatrics, The Medical College of Wisconsin, Milwaukee, Wisconsin, 
      USA.
FAU - Semina, Elena V
AU  - Semina EV
AUID- ORCID: 0000-0003-0531-3586
AD  - Department of Pediatrics, The Medical College of Wisconsin, Milwaukee, Wisconsin, 
      USA.
AD  - Cell Biology, Neurobiology and Anatomy, The Medical College of Wisconsin, 
      Milwaukee, Wisconsin, USA.
AD  - Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, 
      Children's of Wisconsin, Milwaukee, Wisconsin, USA.
AD  - Children's Research Institute, Medical College of Wisconsin, Children's of 
      Wisconsin, Milwaukee, Wisconsin, USA.
LA  - eng
GR  - R01 EY015518/EY/NEI NIH HHS/United States
GR  - R01 EY025718/EY/NEI NIH HHS/United States
GR  - T32 EY014537/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210312
PL  - United States
TA  - Dev Dyn
JT  - Developmental dynamics : an official publication of the American Association of 
      Anatomists
JID - 9201927
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Zebrafish Proteins)
RN  - 0 (mab21l1 protein, zebrafish)
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Cornea/embryology/metabolism
MH  - Embryonic Development/genetics
MH  - Eye/*embryology/metabolism
MH  - Homeodomain Proteins/*genetics/metabolism
MH  - Lens, Crystalline/embryology/metabolism
MH  - Organogenesis/*genetics
MH  - Phenotype
MH  - Zebrafish
MH  - Zebrafish Proteins/*genetics/metabolism
PMC - PMC8349561
MID - NIHMS1724689
OTO - NOTNLM
OT  - IRF1
OT  - LOX
OT  - MAB21L1
OT  - TALEN
OT  - cataracts
OT  - corneal dystrophy
OT  - transcriptome
COIS- DISCLOSURE STATEMENT The authors declare no conflict of interest.
EDAT- 2021/02/12 06:00
MHDA- 2022/03/30 06:00
PMCR- 2022/08/01
CRDT- 2021/02/11 12:13
PHST- 2021/01/28 00:00 [revised]
PHST- 2020/12/05 00:00 [received]
PHST- 2021/02/01 00:00 [accepted]
PHST- 2021/02/12 06:00 [pubmed]
PHST- 2022/03/30 06:00 [medline]
PHST- 2021/02/11 12:13 [entrez]
PHST- 2022/08/01 00:00 [pmc-release]
AID - 10.1002/dvdy.312 [doi]
PST - ppublish
SO  - Dev Dyn. 2021 Aug;250(8):1056-1073. doi: 10.1002/dvdy.312. Epub 2021 Mar 12.