Hardcastle A J, Thiselton D L, Nayudu M, Hampson R M, Bhattacharya S S
Department of Molecular Genetics, Institute of Ophthalmology, London, United Kingdom.
Invest Ophthalmol Vis Sci. 1997 Aug;38(9):1893-6.
To evaluate the role of TIMP-1 in inherited retinal degeneration.
The genomic structure of the TIMP-1 gene was established and male patients with x-linked retinitis pigmentosa 2 from five families were screened for sequence alterations by direct sequencing in all exons, exon-intron boundaries, and the 5' upstream region of the gene.
TIMP-1 appears to be expressed in the retina at low levels and consists of six exons spanning a genomic region of approximately 4.5 kb on Xp11.23. No disease-specific sequence alterations were identified. A site substitution in exon 5 was observed in samples from control subjects and patients, but it did not alter the amino acid sequence of the protein product.
The results of this study exclude mutations in the TIMP-1 coding sequence, splice sites, and the 5' upstream region as a cause of retinal degeneration in x-linked retinitis pigmentosa 2. However, an as yet unidentified regulatory element that lies outside these intervals may be implicated. The role of this tightly regulated protein in the normal functioning of the retina has yet to be determined.
评估金属蛋白酶组织抑制因子-1（TIMP-1）在遗传性视网膜变性中的作用。
确定TIMP-1基因的基因组结构，并通过直接测序对来自五个家系的X连锁视网膜色素变性2型男性患者的所有外显子、外显子-内含子边界及基因的5'上游区域进行序列改变筛查。
TIMP-1似乎在视网膜中低水平表达，由六个外显子组成，跨越Xp11.23上约4.5 kb的基因组区域。未发现疾病特异性序列改变。在对照受试者和患者的样本中均观察到外显子5中的一个位点替换，但它并未改变蛋白质产物的氨基酸序列。
本研究结果排除了TIMP-1编码序列、剪接位点及5'上游区域的突变是X连锁视网膜色素变性2型视网膜变性病因的可能性。然而，可能涉及这些区间之外尚未确定的调控元件。这种受到严格调控的蛋白质在视网膜正常功能中的作用尚待确定。
