In a screen for organogenesis defects in N-ethyl-N-nitrosourea (ENU)-induced mutant mice, we discovered a line carrying a mutation in Colgalt1 [collagen beta(1-O)galactosyltransferase type 1], which is required for proper galactosylation of hydroxylysine residues in a number of collagens. Colgalt1 mutant embryos have not been previously characterized; here, we show that they exhibit skeletal and muscular defects. Analysis of mutant-derived embryonic fibroblasts reveals that COLGALT1 acts on collagen IV and VI, and, while collagen VI appears stable and its secretion is not affected, collagen IV accumulates inside of cells and within the extracellular matrix, possibly due to instability and increased degradation. We also generated mutant zebrafish that do not express the duplicated orthologs of mammalian Colgalt1 The double-homozygote mutants have muscle defects; they are viable through the larvae stage but do not survive to 10 days post-fertilization. We hypothesize that the Colgalt1 mutant could serve as a model of a human connective tissue disorder and/or congenital muscular dystrophy or myopathy.

中文翻译：

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Colgalt1的功能丧失会破坏胶原蛋白的翻译后修饰，并导致肌肉骨骼缺陷。

在对N-乙基-N-亚硝基脲（ENU）诱导的突变小鼠的器官发生缺陷的筛选中，我们发现了在Colgalt1 [胶原β（1-O）半乳糖基转移酶1型]中携带突变的品系，这是适当的半乳糖基化所必需的许多胶原蛋白中的羟赖氨酸残基 Colgalt1突变胚胎以前没有被鉴定过。在这里，我们表明它们表现出骨骼和肌肉缺陷。对突变体来源的胚胎成纤维细胞的分析表明，COLGALT1作用于胶原蛋白IV和VI，尽管胶原蛋白VI看起来稳定且其分泌不受影响，但胶原蛋白IV可能在细胞内部和细胞外基质内积累，可能是由于不稳定和降解增加。我们还产生了不表达哺乳动物Colgalt1直系同源基因的斑马鱼突变体。双纯合子突变体具有肌肉缺陷。它们在幼虫阶段是可行的，但不能存活到受精后10天。我们假设Colgalt1 突变体可以作为人类结缔组织疾病和/或先天性肌营养不良或肌病的模型。