Cell-specific expression of tubby gene family members (tub, Tulp1, 2, and 3) in the retina

Citation
S. Ikeda et al., Cell-specific expression of tubby gene family members (tub, Tulp1, 2, and 3) in the retina, INV OPHTH V, 40(11), 1999, pp. 2706-2712
Citations number
17
Categorie Soggetti
da verificare
Journal title
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
ISSN journal
01460404 → ACNP
Volume
40
Issue
11
Year of publication
1999
Pages
2706 - 2712
Database
ISI
SICI code
0146-0404(199910)40:11<2706:CEOTGF>2.0.ZU;2-0
Abstract
PURPOSE. The family of tubby-like proteins (TULPs), consisting of four fami ly members, ale all expressed in the retina. at varying levels. Mutations w ithin two members, tub and TULP1, are known to lead to retinal degeneration in mouse and humans, respectively, suggesting the functional importance of this family of proteins in the retina. Despite :I high degree of conservat ion in the carboxy-teminal region (eg, putative functional domain of the ge nes) among family members, they are unable to compensate for one another. T he purpose of this study was to provide a rationale for this lack of compen sation by investigating the spatial distribution of tubby gene family membe rs in the retina and to investigate the mechanism of photoreceptor cell dea th in tubby mice. METHODS. In situ hybridization using riboprobes specific fur each tubby gen e family member and immunohistochemistry for TUB and TULP1 were performed t o determine their expression patterns in the retina of tubby and wild-type control mice. The terminal dUTP nick-end labeling (TUNEL) assay was perform ed to detect apoptotic cells in the retina of tubby and wild-type control m ice. RESULTS. tub mRNA was found to be expressed throughout the retina, with hig hest expression in the ganglion cell layer (GCL) and photoreceptor cells. i n contrast, Tulp1 expression was observed only in photoreceptor cells and T ulp3 mRNA was expressed at a moderate level only in the inner nuclear layer (INL) and GCL. The results of the immunohistochemical analysis paralleled those observed in the in situ studies. TUB immunoreactivity was most highly concentrated in the GCL, in the inner and outermost regions of the INL, in the outer plexiform layer (OPL), and in the inner segments of photorecepto r cells. Similarly, TULP1 immunoreactivity was observed in the OPL and inne r segments of the photoreceptor cells. No differences ill expression at the mRNA or protein level were observed for any of the molecules tested in tub by or wild-type mice. TUNEL-positive cells were detected in the ONL of tubb y mice, whereas very few were seen in the same layer of age-matched control mice. CONCLUSIONS. Although all tubby gene family members are expressed in the re tina, they each have different cell-specific expression patterns, which may account in part for their inability to compensate for the loss of one fami ly member. The photoreceptor cell death in tubby mice occurs through an apo ptotic mechanism, which is known to be the common final outcome of other fo rms of retinal degeneration.