Removal of maternal compensation reveals retinal-specific roles for Pomgnt1 in zebrafish
- 1Rutgers Robert Wood Johnson Medical School
Abstract
Genetic variants in Protein O-mannose N-acetylglucosaminyltransferase 1 (POMGNT1) result in a broad spectrum of disorders, ranging from severe congenital muscular dystrophy with brain and ocular malformations to non-syndromic retinitis pigmentosa. Despite POMGNT1's established role in the glycosylation of the transmembrane glycoprotein &alpha-dystroglycan (&alpha-DG), the mechanistic basis for this clinical variability remains poorly understood. Previous work in a zebrafish pomngt1 knock-out (KO) line identified retinal degeneration at 6 months post-fertilization (mpf). However, potential involvement of other tissues was not characterized, and compensation from maternal transcripts which can occur in the zebrafish oocyte was not tested. Here, we analyzed maternal-zygotic pomgnt1 KOs (MZKOs) to determine whether maternal compensation influences the onset and severity of pomgnt1-associated phenotypes. We assessed survival, gross morphology, locomotor activity, behavioral patterns, and retinal organization across multiple timepoints. MZKOs survived to adulthood and exhibited no morphological or locomotor deficits up to 5 mpf. Retinal abnormalities were found as early as 2 mpf in MZKOs, demonstrating that maternally provided factors of pomgnt1 delay the onset of retinal pathology. Additionally, MZKOs displayed a novel wall-hugging behavioral pattern that may be consistent with visual impairment or anxiety. These findings demonstrate a strong tissue-specific phenotype following loss of pomgnt1 in zebrafish showing evolutionary divergence in the necessity for Pomgnt1 function in the muscle. However, this strain provides a useful system for investigating the mechanisms underlying the retinal vulnerability observed in POMGNT1-related retinitis pigmentosa.
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BibTeX
@misc{oliveira2026removal,
title = {{Removal of maternal compensation reveals retinal-specific roles for Pomgnt1 in zebrafish}},
author = {C. D. Oliveira and K. P. Flannery and L. M. Simhon and N. Shi and D. Liu and D. Burbano and M. C. Manzini},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.02.763738},
url = {https://www.biorxiv.org/content/10.64898/2026.11.02.763738v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Removal of maternal compensation reveals retinal-specific roles for Pomgnt1 in zebrafish
AU - C. D. Oliveira
AU - K. P. Flannery
AU - L. M. Simhon
AU - N. Shi
AU - D. Liu
AU - D. Burbano
AU - M. C. Manzini
PY - 2026
DA - 2026/11/02
PB - bioRxiv
DO - 10.64898/2026.11.02.763738
UR - https://www.biorxiv.org/content/10.64898/2026.11.02.763738v1
AB - Genetic variants in Protein O-mannose N-acetylglucosaminyltransferase 1 (POMGNT1) result in a broad spectrum of disorders, ranging from severe congenital muscular dystrophy with brain and ocular malformations to non-syndromic retinitis pigmentosa. Despite POMGNT1's established role in the glycosylation of the transmembrane glycoprotein &alpha-dystroglycan (&alpha-DG), the mechanistic basis for this clinical variability remains poorly understood. Previous work in a zebrafish pomngt1 knock-out (KO) line identified retinal degeneration at 6 months post-fertilization (mpf). However, potential involvement of other tissues was not characterized, and compensation from maternal transcripts which can occur in the zebrafish oocyte was not tested. Here, we analyzed maternal-zygotic pomgnt1 KOs (MZKOs) to determine whether maternal compensation influences the onset and severity of pomgnt1-associated phenotypes. We assessed survival, gross morphology, locomotor activity, behavioral patterns, and retinal organization across multiple timepoints. MZKOs survived to adulthood and exhibited no morphological or locomotor deficits up to 5 mpf. Retinal abnormalities were found as early as 2 mpf in MZKOs, demonstrating that maternally provided factors of pomgnt1 delay the onset of retinal pathology. Additionally, MZKOs displayed a novel wall-hugging behavioral pattern that may be consistent with visual impairment or anxiety. These findings demonstrate a strong tissue-specific phenotype following loss of pomgnt1 in zebrafish showing evolutionary divergence in the necessity for Pomgnt1 function in the muscle. However, this strain provides a useful system for investigating the mechanisms underlying the retinal vulnerability observed in POMGNT1-related retinitis pigmentosa.
ER -