Baseline and innate immune response characterization of a Zfp30 knockout mouse strain
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Baseline and innate immune response characterization of a Zfp30 knockout mouse strain Lucas T. Laudermilk1,2 · Adelaide Tovar1,2 · Alison K. Homstad1,2 · Joseph M. Thomas1 · Kathryn M. McFadden1 · Miriya K. Tune3 · Dale O. Cowley1,4 · Jason R. Mock3 · Folami Ideraabdullah1,2,5 · Samir N. P. Kelada1,2,3 Received: 25 June 2020 / Accepted: 17 August 2020 / Published online: 29 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Airway neutrophilia is correlated with disease severity in a number of chronic and acute pulmonary diseases, and dysregulation of neutrophil chemotaxis can lead to host tissue damage. The gene Zfp30 was previously identified as a candidate regulator of neutrophil recruitment to the lungs and secretion of CXCL1, a potent neutrophil chemokine, in a genome-wide mapping study using the Collaborative Cross. ZFP30 is a putative transcriptional repressor with a KRAB domain capable of inducing heterochromatin formation. Using a CRISPR-mediated knockout mouse model, we investigated the role that Zfp30 plays in recruitment of neutrophils to the lung using models of allergic airway disease and acute lung injury. We found that the Zfp30 null allele did not affect CXCL1 secretion or neutrophil recruitment to the lungs in response to various innate immune stimuli. Intriguingly, despite the lack of neutrophil phenotype, we found there was a significant reduction in the proportion of live Zfp30 homozygous female mutant mice produced from heterozygous matings. This deviation from the expected Mendelian ratios implicates Zfp30 in fertility or embryonic development. Overall, our results indicate that Zfp30 is an essential gene but does not influence neutrophilic inflammation in this particular knockout model.
Introduction Neutrophils are key participants in the innate immune system’s response to pathogens, but the mechanisms by which these cells respond to immune challenge are prone to generating collateral host tissue damage (Nathan 2006). This makes regulation of neutrophil chemotaxis particularly Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00335-020-09847-z) contains supplementary material, which is available to authorized users. * Samir N. P. Kelada [email protected] 1
Department of Genetics, University of North Carolina, 120 Mason Farm Road, Chapel Hill, NC 27599, USA
2
Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA
3
Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA
4
Animal Models Core Facility, University of North Carolina, Chapel Hill, NC, USA
5
Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA
important in defending against outside insults and preventing unwanted organ damage. This signaling balance is particularly vital in the lungs due to the continual exposure to pathogens, allergens, and other environmental exposures that are introduced through respiration. Dysregulation of the chem
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