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Baseline and innate immune response characterization of a Zfp30 knockout mouse strain.
Mammalian Genome ( IF 2.7 ) Pub Date : 2020-08-29 , DOI: 10.1007/s00335-020-09847-z
Lucas T Laudermilk 1, 2 , Adelaide Tovar 1, 2 , Alison K Homstad 1, 2 , Joseph M Thomas 1 , Kathryn M McFadden 1 , Miriya K Tune 3 , Dale O Cowley 1, 4 , Jason R Mock 3 , Folami Ideraabdullah 1, 2, 5 , Samir N P Kelada 1, 2, 3
Affiliation  

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.



中文翻译:

Zfp30 敲除小鼠品系的基线和先天免疫反应表征。

在许多慢性和急性肺部疾病中,气道中性粒细胞增多与疾病严重程度相关,中性粒细胞趋化性失调可导致宿主组织损伤。在使用 Collaborative Cross 进行的全基因组作图研究中,基因Zfp30先前被确定为肺中性粒细胞募集和 CXCL1(一种有效的中性粒细胞趋化因子)分泌的候选调节剂。ZFP30 是一种推定的转录抑制因子,具有能够诱导异染色质形成的 KRAB 结构域。使用 CRISPR 介导的敲除小鼠模型,我们使用过敏性气道疾病和急性肺损伤模型研究了Zfp30在将嗜中性粒细胞募集到肺中所起的作用。我们发现Zfp30无效等位基因不影响响应各种先天免疫刺激的CXCL1分泌或中性粒细胞向肺的募集。有趣的是,尽管缺乏中性粒细胞表型,我们发现杂合交配产生的活Zfp30纯合雌性突变小鼠的比例显着降低。这种与预期孟德尔比率的偏差表明 Zfp30与生育力或胚胎发育有关。总体而言,我们的结果表明Zfp30是一个必需基因,但在这个特定的敲除模型中不影响中性粒细胞炎症。

更新日期:2020-08-29
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