Siracusa L D, McGrath R, Ma Q, Moskow J J, Manne J, Christner P J, Buchberg A M, Jimenez S A
Department of Microbiology and Immunology, Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541, USA.
Genome Res. 1996 Apr;6(4):300-13. doi: 10.1101/gr.6.4.300.
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 1 (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.
携带紧密皮肤（Tsk）突变的小鼠由于细胞外基质分子的积累而出现皮肤增厚和内脏纤维化。这些以及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。此前我们将Tsk定位到小鼠2号染色体上与人类15号染色体同线的区域。人类15号染色体q上的微原纤维糖蛋白基因，即原纤蛋白1（FBN1），成为Tsk突变的一个候选基因。我们现在证明，Tsk染色体在Fbn1基因内存在一个30至40kb的基因组重复，导致产生一个比正常读框更大的Fbn1转录本。这些发现为解释Tskl +小鼠的一些表型特征以及Tsk/Tsk胚胎的致死性提供了假设。
