Extensive variation in the intelectin gene family in laboratory and wild mouse strains.

Extensive variation in the intelectin gene family in laboratory and wild mouse strains.
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在实验室和野鼠品系中intelectin基因家族的广泛变异。

DOI:
10.1038/s41598-021-94679-3
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发表时间:
2021-07-30
期刊:
影响因子:
4.6
通讯作者:
Hollox EJ
Hollox EJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Almalki F;Nonnecke EB;Castillo PA;Bevin-Holder A;Ullrich KK;Lönnerdal B;Odenthal-Hesse L;Bevins CL;Hollox EJ

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白细胞凝集素是一个多聚体分泌蛋白质家族,其结合微生物特异性聚糖。遗传和功能研究都表明,intelectins在先天免疫中具有重要作用,并参与各种人类疾病的病因学,包括炎症性肠病。使用小鼠模型研究intelectin在人类疾病中的作用的实验受到以下事实的限制:人类和小鼠中的intelectin基因之间没有明确的一对一关系,并且intelectin基因的数量在不同的小鼠品系之间变化。在这项研究中,我们通过基因序列和基因表达分析表明,人类intelectin-1(ITLN 1)在小鼠中有多个直系同源物,包括功能同源物Itln 1;然而,人类intelectin-2没有这样的直系同源物或同源物。我们证实,所有的C57小鼠品系的亚株有一个大的删除,导致保留只有一个intelectin基因,Itln 1。除了CAST、SPRET、SKIVE、MOLF和PANCEVO品系之外,大多数实验室品系都具有完整的六种intelectin基因,这些品系来源于不同的小鼠种属/亚种,编码不同的intelectin基因。在野生小鼠中,在Mus musculus castaneus和Mus musculus sputicus中intelectin缺失是多态的。进一步的序列分析表明,Itln 3和Itln 5是多态性假基因,由于过早截断突变,和小鼠Itln 1经历了最近的适应性进化。总之,我们的研究表明,实验室和野生小鼠的intelectin基因存在广泛的多样性,这表明了出生和死亡的进化模式。此外,我们的数据提供了一个基础,进一步的实验研究的作用,intelectins在疾病。
Intelectins are a family of multimeric secreted proteins that bind microbe-specific glycans. Both genetic and functional studies have suggested that intelectins have an important role in innate immunity and are involved in the etiology of various human diseases, including inflammatory bowel disease. Experiments investigating the role of intelectins in human disease using mouse models are limited by the fact that there is not a clear one-to-one relationship between intelectin genes in humans and mice, and that the number of intelectin genes varies between different mouse strains. In this study we show by gene sequence and gene expression analysis that human intelectin-1 (ITLN1) has multiple orthologues in mice, including a functional homologue Itln1; however, human intelectin-2 has no such orthologue or homologue. We confirm that all sub-strains of the C57 mouse strain have a large deletion resulting in retention of only one intelectin gene, Itln1. The majority of laboratory strains have a full complement of six intelectin genes, except CAST, SPRET, SKIVE, MOLF and PANCEVO strains, which are derived from different mouse species/subspecies and encode different complements of intelectin genes. In wild mice, intelectin deletions are polymorphic in Mus musculus castaneus and Mus musculus domesticus. Further sequence analysis shows that Itln3 and Itln5 are polymorphic pseudogenes due to premature truncating mutations, and that mouse Itln1 has undergone recent adaptive evolution. Taken together, our study shows extensive diversity in intelectin genes in both laboratory and wild-mice, suggesting a pattern of birth-and-death evolution. In addition, our data provide a foundation for further experimental investigation of the role of intelectins in disease.
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发表时间: 2010-12
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期刊: SCIENTIFIC DATA
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