Hinsdale M E, Kelly C L, Wood P A
Department of Comparative Medicine, School of Medicine, University of Alabama, Birmingham 35294-0019.
Genomics. 1993 Jun;16(3):605-11. doi: 10.1006/geno.1993.1237.
BALB/cByJ mice have a deficiency of short-chain acyl-CoA dehydrogenase (SCAD), an enzyme of fatty acid beta-oxidation. This mutant mouse strain represents the only animal model for any human inborn error of fatty acid metabolism. We have investigated the molecular basis of this defect by DNA and RNA analyses, comparing these mice with the wild-type predecessor strain BALB/cBy. We found that the mutant strain has a 278-bp deletion in the 3' end of the structural gene for SCAD and reduced steady-state levels of SCAD mRNA. Two major transcripts are produced in the mutant. One contains intronic sequence due to the absence of splicing, and the second transcript results from missplicing of a normal splice donor site to a cryptic splice acceptor site in the 3' terminal exon. Both abnormal transcripts have aberrant stop codons. These results demonstrate the molecular basis of SCAD deficiency in this unique mouse model.
BALB/cByJ小鼠缺乏短链酰基辅酶A脱氢酶（SCAD），这是一种脂肪酸β氧化酶。这种突变小鼠品系是人类脂肪酸代谢先天性缺陷的唯一动物模型。我们通过DNA和RNA分析研究了这种缺陷的分子基础，将这些小鼠与野生型亲本品系BALB/cBy进行了比较。我们发现突变品系在SCAD结构基因的3'端有一个278 bp的缺失，并且SCAD mRNA的稳态水平降低。突变体产生两种主要转录本。一种由于缺乏剪接而包含内含子序列，第二种转录本是由于正常剪接供体位点与3'末端外显子中一个隐蔽的剪接受体位点错配剪接产生的。两种异常转录本都有异常的终止密码子。这些结果证明了这种独特小鼠模型中SCAD缺乏的分子基础。
