Tubby-like protein 1 (Tulp1) is required for normal photoreceptor synaptic development.

Mutations in the photoreceptor-specific tubby-like protein 1 (TULP1) underlie a form of autosomal recessive retinitis pigmentosa in humans and photoreceptor degeneration in mice. In wild type (wt) mice, Tulp1 is localized to the photoreceptor inner segment, connecting cilium and synapse. To investigate the role of Tulp1 in the synapse, we examined the pre- and postsynaptic architecture in tulp1-/- mice. We used immunohistochemistry to examine tulp1-/- mice prior to retinal degeneration and made comparisons to wt littermates and rd10 mice. In the tulp1-/- synapse, the spatial relationship between the ribbon-associated proteins, Bassoon and Piccolo, are disrupted, and few intact ribbons are present. Furthermore, bipolar cell dendrites are stunted, most likely a direct consequence of the malformed photoreceptor synapses. Comparable abnormalities are not seen in rd10 mice. The association of early onset and severe photoreceptor degeneration, which is preceded by synaptic abnormalities, appears to represent a phenotype not previously described. Our new evidence indicates that Tulp1 is not only critical for photoreceptor function and survival, but is essential for the proper development of the photoreceptor synapse.