The Col4a2em1(IMPC)Wtsi mouse line: lessons from the Deciphering the Mechanisms of Developmental Disorders program
The Col4a2em1(IMPC)Wtsi mouse line: lessons from the Deciphering the Mechanisms of Developmental Disorders program
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DOI：
10.1242/bio.042895
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发表时间：
2019-08-01
期刊：
影响因子：
2.4
通讯作者：
Weninger, Wolfgang J.
中科院分区：
文献类型：
--
作者：
Reissig, Lukas F.;Herdina, Anna Nele;Weninger, Wolfgang J.
发育障碍机制的破译（DMDD）项目使用系统和标准化的方法来描述源自小鼠系的胚胎的表型，这些胚胎产生胚胎致命的后代。我们的研究旨在提供在DMDD中产生并在胚胎14.5天收获的纯合子Col4a2（em1(IMPC)Wtsi）突变体的详细表型描述。这将为Col4a2在器官发生中的作用提供新的信息，并证明DMDD数据库在确定遗传疾病研究模型方面的能力。DMDD Col4a2（em1(IMPC)Wtsi）突变体在器官发生中存活下来，从而揭示了器官和组织的全谱，其发育依赖于Col4a2编码蛋白。他们表现出大脑、脑神经、视觉系统、肺、内分泌腺、骨骼、上皮下组织和轻度至重度心血管畸形的缺陷。总之，这使得DMDD Col4a2（em1(IMPC)Wtsi）线成为鉴定缺陷谱和研究常染色体显性脑空畸形2(omim# 614483)（一种罕见的人类疾病）的潜在机制的有用模型。因此，我们证明了DMDD方法和网页作为识别罕见疾病小鼠模型的有价值来源的一般能力。
The Deciphering the Mechanisms of Developmental Disorders (DMDD) program uses a systematic and standardised approach to characterise the phenotype of embryos stemming from mouse lines, which produce embryonically lethal offspring. Our study aims to provide detailed phenotype descriptions of homozygous Col4a2(em1(IMPC)Wtsi) mutants produced in DMDD and harvested at embryonic day 14.5. This shall provide new information on the role Col4a2 plays in organogenesis and demonstrate the capacity of the DMDD database for identifying models for researching inherited disorders. The DMDD Col4a2(em1(IMPC)Wtsi) mutants survived organogenesis and thus revealed the full spectrum of organs and tissues, the development of which depends on Col4a2 encoded proteins. They showed defects in the brain, cranial nerves, visual system, lungs, endocrine glands, skeleton, subepithelial tissues and mild to severe cardiovascular malformations. Together, this makes the DMDD Col4a2(em1(IMPC)Wtsi) line a useful model for identifying the spectrum of defects and for researching the mechanisms underlying autosomal dominant porencephaly 2 (OMIM # 614483), a rare human disease. Thus we demonstrate the general capacity of the DMDD approach and webpage as a valuable source for identifying mouse models for rare diseases.