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Sakae Ikeda, Wei He, Akihiro Ikeda, Jürgen K. Naggert, Michael A. North, Patsy M. Nishina; Cell-Specific Expression of Tubby Gene Family Members (tub, Tulp1, 2, and 3) in the Retina. Invest. Ophthalmol. Vis. Sci. 1999;40(11):2706-2712.
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purpose. The family of tubby-like proteins (TULPs), consisting of four family
members, are all expressed in the retina at varying levels. Mutations
within 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 a high degree of conservation in the
carboxy-teminal region (e.g., putative functional domain of the genes)
among family members, they are unable to compensate for one another.
The purpose of this study was to provide a rationale for this lack of
compensation by investigating the spatial distribution of tubby gene
family members in the retina and to investigate the mechanism of
photoreceptor cell death in tubby mice.
methods. In situ hybridization using riboprobes specific for each tubby gene
family member and immunohistochemistry for TUB and TULP1 were performed
to determine their expression patterns in the retina of tubby and
wild-type control mice. The terminal dUTP nick-end labeling (TUNEL)
assay was performed to detect apoptotic cells in the retina of tubby
and wild-type control mice.
results. tub mRNA was found to be expressed throughout the
retina, with highest expression in the ganglion cell layer (GCL) and
photoreceptor cells. In contrast, Tulp1 expression was
observed only in photoreceptor cells and Tulp3 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
photoreceptor cells. Similarly, TULP1 immunoreactivity was observed in
the OPL and inner segments of the photoreceptor cells. No differences
in expression at the mRNA or protein level were observed for any of the
molecules tested in tubby or wild-type mice. TUNEL-positive cells were
detected in the ONL of tubby 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 retina,
they each have different cell-specific expression patterns, which may
account in part for their inability to compensate for the loss of one
family member. The photoreceptor cell death in tubby mice occurs
through an apoptotic mechanism, which is known to be the common final
outcome of other forms of retinal
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