A tandem duplication within the fibrillin 1 gene is associated with the mouse tight skin mutation
A tandem duplication within the fibrillin 1 gene is associated with the mouse tight skin mutation
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DOI：
10.1101/gr.6.4.300
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发表时间：
1996-04-01
期刊：
影响因子：
7
通讯作者：
Jimenez, SA
中科院分区：
文献类型：
--
作者：
Siracusa, LD;McGrath, R;Jimenez, SA
携带Tight skin（Tsk）突变的小鼠由于细胞外基质分子的积累而具有增厚的皮肤和内脏纤维化。这些和其他结缔组织异常使得Tskl +小鼠成为硬皮病、遗传性肺气肿和心肌肥大的模型。以前，我们本地化的Tsk小鼠2号染色体在一个区域与人类15号染色体同线。位于人类染色体15 q上的微纤维糖蛋白基因-我们现在证明，Tsk染色体在Fbn 1基因内含有30- 40-kb的基因组重复，导致比正常的框内Fbn 1转录本更大。这些发现提供了解释Tskl +小鼠的一些表型特征和Tsk/Tsk胚胎致死率的假设。
Mice carrying the Tight skin (Tsk) mutation have thickened skin and visceral fibrosis resulting from an accumulation of extracellular matrix molecules. These and other connective tissue abnormalities have made Tskl + mice models for scleroderma, hereditary emphysema, and myocardial hypertrophy. Previously we localized Tsk to mouse chromosome 2 in a region syntenic with human chromosome 15. The microfibrillar glycoprotein gene, fibrillin I (FBN1), on human chromosome 15q, provided a candidate for the Tsk mutation. We now demonstrate that the Tsk chromosome harbors a 30- to 40-kb genomic duplication within the Fbn1 gene that results in a larger than normal in-frame Fbn1 transcript. These Findings provide hypotheses to explain some of the phenotypic characteristics of Tskl + mice and the lethality of Tsk/Tsk embryos.