Journal article
The transcriptional regulator GON4L is required for viability and hematopoiesis in mice
Experimental hematology, Vol.98, pp.25-35
06/01/2021
DOI: 10.1016/j.exphem.2021.04.001
PMCID: PMC8184620
PMID: 33864850
Abstract
The Gon4l gene encodes a putative transcriptional regulator implicated in the control of both cell differentiation and proliferation. Previously, we described a mutant mouse strain called Just), in which splicing of pre-mRNA generated from Gon4l is disrupted. This defect severely reduces, but does not abolish, GON4L protein expression and blocks the formation of early B-lineage progenitors, suggesting Gon4l is required for B-cell development in vertebrates. Yet, mutations that disable Gon4l in zebrafish impair several facets of embryogenesis that include the initiation of primitive hematopoiesis, arguing this gene is needed for multiple vertebrate developmental pathways. To better understand the importance of Gon4l in mammals, we created mice carrying an engineered version of Gon4l that can be completely inactivated by Cre-mediated recombination. Breeding mice heterozygous for the inactivated Gon4l allele failed to yield any homozygous-null offspring, indicating Gon4l is an essential gene in mammals. Consistent with this finding, as well previously published results, cell culture studies revealed that loss of Gon4l blocks cell proliferation and compromises viability, suggesting a fundamental role in the control of cell division and survival. Studies using mixed bone marrow chimeras confirmed Gon4l is required for B-cell development but also found it is needed to maintain definitive hematopoietic stem/progenitor cells that are the source of all hematopoietic cell lineages. Our findings reveal Gon4l is an essential gene in mammals that is required to form the entire hematopoietic system. (C) 2021 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.
Details
- Title: Subtitle
- The transcriptional regulator GON4L is required for viability and hematopoiesis in mice
- Creators
- Diana F. Colgan - Roy J. and Lucille A. Carver College of MedicineRenee X. Goodfellow - Roy J. and Lucille A. Carver College of MedicineJohn D. Colgan - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Experimental hematology, Vol.98, pp.25-35
- Publisher
- Elsevier
- DOI
- 10.1016/j.exphem.2021.04.001
- PMID
- 33864850
- PMCID
- PMC8184620
- ISSN
- 0301-472X
- eISSN
- 1873-2399
- Number of pages
- 11
- Grant note
- AI093737 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Carver College of Medicine RR027219 / National Center for Research Resources of the NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) Iowa City Veteran's Administration Medical Center Holden Comprehensive Cancer Center
- Language
- English
- Date published
- 06/01/2021
- Academic Unit
- Anatomy and Cell Biology; Immunology; Otolaryngology; Internal Medicine
- Record Identifier
- 9984284336102771
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