The Expression Of TTC4 Gene In Normal Human Eye Tissue

Background: Deletions of the short arm of chromosome 1 are among the most frequent aberrations in many solid tumors including neuroblastoma, breast cancer and malignant melanoma of the skin. In particular, loss of heterozygosity for the chromosome 1p31 region han been reported in up to 50% of human breast cancers, indicating the presence of a tumor suppressor gene in this location. In 1999, a novel human gene which belongs to TTC gene family has been mapped in this region of the short arm of chromosome 1 and named TTC4. In 2000, the exon/intron structure of TTC4 has been reported .This gene encodes a transcript of 2.1kb and contains 4 TPR motifs and a coiled-coil domain. Sequence alignment identified ten exons. Although the function of TTC4 is not known, it might be predicted to have some interesting functions related to tumorigenesis because of its relatedness to other TTC motif genes. In November 2000 TTC4 gene mutation in malignant melanoma of the skin was identified in a German lab which indicated TTC4 may be a candidate tumor suppressor gene. On account of tumorigenesis resulted from the inactivity of TTC4 gene, it might be predicted that TTC4 may play an important role in the pathogenesis of malignant melanomas. Northern blot analysis of the distribution of tissue of TTC4 gene expression shows that it could be detectable at high levels in heart, brain, placenta, liver, skeletal muscle, kidney and pancreas, but low levels in lung. Theoretically each gene isolated from the region of LOH on chromosome should represent a candidate tumor suppressor gene .Thus, segregating these genes is helpful to understand the mechanism of tumorigesis. Objective: to explore the expression of TTC4 gene in normal human eye tissue and the difference among different parts of eye tisse. Methods: FISH methods was used. To design and synthesize probe labled with fluorescene in 5'end on the basis of TTC4 gene sequence, hybridize fluorescene-labled probe with paraffin sample of human eye tissue. The expression of TTC4 gene was observed in green colour at the wavelength of 450nm-540nm under confocal laser scanning microscope. Results: In normal human eye tissue, the TTC4 transcripts were detected in ciliary body, choroids and sclera with stronger signal. Retinal pigment epithelium, inner nuclear layer, outter nuclear layer and inner limiting membrane were positive. Our findings indicated TTC4 gene may participate the normal development and function of human eye tissue.