Socs3b regulates the development and function of innate immune cells in zebrafish

Sobah, Mohamed L.; Scott, Aimee C.; Laird, Miranda; Koole, Cassandra; Liongue, Clifford; Ward, Alister C.

doi:10.3389/fimmu.2023.1119727

Cited by 4 publications

(10 citation statements)

References 83 publications

(103 reference statements)

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“…We have recently generated a Stat3 knockout (KO) zebrafish mutant, containing a frameshift and early stop codon in the N-terminal domain leading to a severely truncated protein, as well as a mutant with a frameshift and early stop codon toward the end of the SH2 domain resulting in complete transactivation domain truncation (ΔTAD) (Sobah, M.L., et al, 2024 [ 28 ]). Homozygous Stat3 KO and ΔTAD mutants were both noticeably smaller than their wildtype (WT) counterparts ( Figure 1 A–C).…”

Section: Resultsmentioning

confidence: 99%

“…Stat3 wildtype (WT), knockout (KO, mdu35 ), and transactivation domain truncation (ΔTAD, mdu36 ) zebrafish alleles were generated in-house (Sobah, M.L., et al, 2024 [ 28 ]) and crossed onto the Tg( mpeg1.1 :GFP) [ 57 ] and Tg( mpx :GFP) [ 58 ] backgrounds obtained directly from their respective laboratories of origin. All lines were maintained using standard husbandry practices in a purpose-built aquarium (Tecniplast, West Chester, PA, USA) on a 14/10 h light/dark cycle with twice-daily feeding.…”

Section: Methodsmentioning

confidence: 99%

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Contribution of Signal Transducer and Activator of Transcription 3 (STAT3) to Bone Development and Repair

Sobah,

Liongue,

Ward

2023

IJMS

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Signal transducer and activator of transcription 3 (STAT3) is a transcription factor activated canonically by numerous cytokines and other factors, with significant roles in immunity, immune diseases, and cancer. It has also been implicated in several human skeletal disorders, with loss-of-function (LOF) mutations associated with aberrant skeletal development. To gain further insights, two zebrafish STAT3 lines were investigated: a complete LOF knockout (KO) mutant and a partial LOF mutant with the transactivation domain truncated (ΔTAD). Consistent with other studies, the KO mutants were smaller, with reduced length in early embryos exacerbated by a decreased growth rate from 5 days postfertilization (dpf). They displayed skeletal deformities that approached 80% incidence by 30 dpf, with a significant reduction in early bone but not cartilage formation. Further analysis additionally identified considerable abrogation of caudal fin regeneration, concomitant with a paucity of infiltrating macrophages and neutrophils, which may be responsible for this. Most of these phenotypes were also observed in the ΔTAD mutants, indicating that loss of canonical STAT3 signaling was the likely cause. However, the impacts on early bone formation and regeneration were muted in the ΔTAD mutant, suggesting the potential involvement of noncanonical functions in these processes.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Contribution of Signal Transducer and Activator of Transcription 3 (STAT3) to Bone Development and Repair

Sobah,

Liongue,

Ward

2023

IJMS

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“…Alternatively, 100 ng/µL mRNA encoding the zebrafish granulocyte colony-stimulating factor (G-CSF) paralogue, Csf3a, in 1 × Danieau buffer containing 1% (w/v) phenol red was injected into 1 cell stage embryos [ 38 ] with imaging or RNA extraction performed at 3 dpf. Neutrophil and macrophage migration was assessed using a wound healing assay [ 39 ]. Transgenic embryos at 3 dpf were anaesthetized with 5 μg/mL benzocaine in E3/PTU before the excision of their caudal fin, with the injury site imaged at 4 h intervals using fluorescence microscopy.…”

Section: Methodsmentioning

confidence: 99%

Stat3 Regulates Developmental Hematopoiesis and Impacts Myeloid Cell Function via Canonical and Non-Canonical Modalities

Sobah,

Liongue,

Ward

2024

J Innate Immun

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Signal transducer and activator of transcription (STAT) 3 is extensively involved in the development, homeostasis and function of immune cells, with STAT3 disruption associated with human immune-related disorders. These roles have been assumed to be due to its canonical mode of action as an inducible transcription factor downstream of multiple cytokines, although alternative non-canonical functional modalities have also been described for STAT3. To further understand the roles of STAT3 gained from lineage-specific mouse knockouts, CRISPR/Cas9 was used to generate mutants of the conserved zebrafish Stat3 protein: a loss of function knockout (KO) mutant and a mutant lacking C-terminal sequences including the transactivation domain (ΔTAD). Analysis of the KO mutant identified conserved roles for Stat3 within hematopoietic stem cells impacting the development of all lineages throughout primitive and early definitive hematopoiesis, with altered immune cell populations in juveniles. The Stat3 KO mutant was unable to respond to lipopolysaccharide (LPS) or granulocyte colony-stimulating factor (G-CSF), and also exhibited significantly diminished neutrophil migration that correlated with abrogation of the Cxcl8b/Cxcr2 pathway. Many of these phenotypes were not shared by the Stat3 ΔTAD mutant. Indeed, only neutrophil and macrophage development were disrupted in these mutants with neutrophil migration actually increased, while responsiveness to LPS and G-CSF was maintained. This suggests that Stat3 participates in innate immune cell development and function through both canonical and non-canonical modalities, providing additional insights for relevant diseases.

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“…The targets of studies include lysosomes [ 170 , 171 ], endoplasmic reticulum [ 172 ], membranes [ 173 ], membrane channels [ 174 ], cytoskeleton [ 175 ], recombination processes [ 176 ], aneuploidy [ 177 ], expression regulation [ 178 ], and signaling [ 179 ]. There is research on the genetic basis of the organism’s response to oxidative stress [ 180 , 181 , 182 , 183 , 184 ], hypoxia [ 185 , 186 , 187 ], sodium ion uptake from the surrounding aquatic environment and ammonia excretion [ 188 , 189 , 190 ], inflammation processes [ 191 , 192 ], immunity [ 193 , 194 , 195 , 196 ] and disease resistance [ 197 , 198 , 199 , 200 , 201 ].…”

Section: Genome Editing In Salmonidae and Cyprinidae Aquaculture Fish...mentioning

confidence: 99%

“…The gpr56 gene coordinates the expression of other immune response genes and digestive enzyme genes [ 193 ]. The socs3b , mitfa , CD18 , and lcp1 genes control the morphology, number, or migration of neutrophils and macrophages to the site of inflammation [ 154 , 159 , 194 , 195 ]. Knockout mutants of the fam76b gene produce hyperinflammation in response to antigen activity [ 337 ].…”

Section: Genome Editing In Salmonidae and Cyprinidae Aquaculture Fish...mentioning

confidence: 99%

In Search of a Target Gene for a Desirable Phenotype in Aquaculture: Genome Editing of Cyprinidae and Salmonidae Species

Orlova,

Ruzina,

Emelianova

et al. 2024

Genes

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Aquaculture supplies the world food market with a significant amount of valuable protein. Highly productive aquaculture fishes can be derived by utilizing genome-editing methods, and the main problem is to choose a target gene to obtain the desirable phenotype. This paper presents a review of the studies of genome editing for genes controlling body development, growth, pigmentation and sex determination in five key aquaculture Salmonidae and Cyprinidae species, such as rainbow trout (Onchorhynchus mykiss), Atlantic salmon (Salmo salar), common carp (Cyprinus carpio), goldfish (Carassius auratus), Gibel carp (Carassius gibelio) and the model fish zebrafish (Danio rerio). Among the genes studied, the most applicable for aquaculture are mstnba, pomc, and acvr2, the knockout of which leads to enhanced muscle growth; runx2b, mutants of which do not form bones in myoseptae; lepr, whose lack of function makes fish fast-growing; fads2, Δ6abc/5Mt, and Δ6bcMt, affecting the composition of fatty acids in fish meat; dnd mettl3, and wnt4a, mutants of which are sterile; and disease-susceptibility genes prmt7, gab3, gcJAM-A, and cxcr3.2. Schemes for obtaining common carp populations consisting of only large females are promising for use in aquaculture. The immobilized and uncolored zebrafish line is of interest for laboratory use.

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Socs3b regulates the development and function of innate immune cells in zebrafish

Cited by 4 publications

References 83 publications

Contribution of Signal Transducer and Activator of Transcription 3 (STAT3) to Bone Development and Repair

Contribution of Signal Transducer and Activator of Transcription 3 (STAT3) to Bone Development and Repair

Stat3 Regulates Developmental Hematopoiesis and Impacts Myeloid Cell Function via Canonical and Non-Canonical Modalities

In Search of a Target Gene for a Desirable Phenotype in Aquaculture: Genome Editing of Cyprinidae and Salmonidae Species

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