小柯机器人

美国科罗拉多大学Joaquin M. Espinosa等研究人员合作发现，干扰素受体位点的三倍化促进小鼠模型中的唐氏综合征特征。相关论文于2023年6月5日在线发表在《自然—遗传学》杂志上。

研究人员证明，21号染色体上的干扰素受体（IFNR）基因簇的三倍化是唐氏综合征（DS）小鼠模型中多种表型所需的。全血转录组分析表明，IFNR的过度表达与DS患者的慢性干扰素过度活动和炎症有关。为了确定该基因座对DS表型的贡献，研究人员使用基因组编辑来纠正了DS小鼠模型中的拷贝数，这使抗病毒反应正常化，防止心脏畸形，改善发育迟缓，并提高认知能力和减轻颅面异常。Ifnr基因座的三倍化调节了小鼠DS的特征，这表明21三体引起的干扰素病可能适合于治疗干预。

据了解，DS是由21三体引起的遗传病，其特点是不同的认知障碍、免疫失调、形态失调和不同并发症的发生率增加。21三体综合征引起这些影响的机制在很大程度上仍然是未知的。

附：英文原文

Title: Triplication of the interferon receptor locus contributes to hallmarks of Down syndrome in a mouse model

Author: Waugh, Katherine A., Minter, Ross, Baxter, Jessica, Chi, Congwu, Galbraith, Matthew D., Tuttle, Kathryn D., Eduthan, Neetha P., Kinning, Kohl T., Andrysik, Zdenek, Araya, Paula, Dougherty, Hannah, Dunn, Lauren N., Ludwig, Michael, Schade, Kyndal A., Tracy, Dayna, Smith, Keith P., Granrath, Ross E., Busquet, Nicolas, Khanal, Santosh, Anderson, Ryan D., Cox, Liza L., Estrada, Belinda Enriquez, Rachubinski, Angela L., Lyford, Hannah R., Britton, Eleanor C., Fantauzzo, Katherine A., Orlicky, David J., Matsuda, Jennifer L., Song, Kunhua, Cox, Timothy C., Sullivan, Kelly D., Espinosa, Joaquin M.

Issue&Volume: 2023-06-05

Abstract: Down syndrome (DS), the genetic condition caused by trisomy 21, is characterized by variable cognitive impairment, immune dysregulation, dysmorphogenesis and increased prevalence of diverse co-occurring conditions. The mechanisms by which trisomy 21 causes these effects remain largely unknown. We demonstrate that triplication of the interferon receptor (IFNR) gene cluster on chromosome 21 is necessary for multiple phenotypes in a mouse model of DS. Whole-blood transcriptome analysis demonstrated that IFNR overexpression associates with chronic interferon hyperactivity and inflammation in people with DS. To define the contribution of this locus to DS phenotypes, we used genome editing to correct its copy number in a mouse model of DS, which normalized antiviral responses, prevented heart malformations, ameliorated developmental delays, improved cognition and attenuated craniofacial anomalies. Triplication of the Ifnr locus modulates hallmarks of DS in mice, suggesting that trisomy 21 elicits an interferonopathy potentially amenable to therapeutic intervention. A mouse model of Down syndrome (DS) highlights the importance of triplication of the IFNR gene cluster for a variety of DS-associated traits. Copy number correction resulted in amelioration of multiple phenotypes associated with the condition.

DOI: 10.1038/s41588-023-01399-7

Source: https://www.nature.com/articles/s41588-023-01399-7

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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