which form synaptic contacts with dendrites of second order neurons in the outer plexiform layer (OPL) (Hagstrom et al. 1999; Ikeda et al. 2000; Hagstrom et al. 2001). Tulp1 is a cytoplasmic protein that associates with cellular membranes and the actin cytoskeleton (Xi et al. 2005). In tulp1–/– mice, there is an early-onset progressive photoreceptor degeneration, rod and cone opsins are mislocalized, and rhodopsin-bearing extracellular vesicles accumulate around the ellipsoid region of the IS (Hagstrom et al. 1999). These defects indicate that Tulp1 may be involved in actin cytoskeletal dynamics such as protein transport from the IS to the outer segment (OS) via the CC (Hagstrom et al. 1999; 2001; Xi et al. 2005; 2007). Additional evidence signifies that Tulp1 may also be involved in membrane dynamics at the highly active photoreceptor synapse. We have shown that Tulp1 co-localizes with and binds to the neuronal-specific protein Dynamin-1 at the IS and the photoreceptor terminals (Xi et al. 2007). Dynamin-1 is a GTPase that also binds actin and regulates vesicle movement at the trans-Golgi network, the plasma membrane and the synaptic membrane (van der Bliek 1999; McNiven et al. 2000; Xi et al. 2007). Furthermore, the b-wave component of the electroretinogram (ERG) generated by depolarizing bipolar cells (DBCs) is markedly reduced in young tulp1–/– mice, indicating an alteration in synaptic communication in the absence of Tulp1 (Xi et al. 2007). Based upon these findings, we hypothesize that Tulp1 plays a role in synaptic function.

In the present study, we examined the architecture of the tulp1–/– synapse at P16, an age at which synaptic development is complete in wild type (wt) mice (Dick et al. 2003), but precedes photoreceptor degeneration in tulp1–/– mice (Hagstrom et al. 1999). To test whether synaptic alterations are specific to the tulp1–/– retina and not a consequence of a generalized retinal degeneration, parallel studies were conducted in the retinal degeneration 10 (rd10) mouse, a mouse model of retinal degeneration due to a different molecular defect (Chang et al. 2002). These mice have a comparable rate of photoreceptor degeneration but do not exhibit early synaptic defects (Chang et al. 2007; Gargini et al. 2007). We show that at an early age, tulp1–/– mice lack the tight coupling between the ribbon-associated proteins, Bassoon and Piccolo, and few intact ribbons are present. In addition, dendrites of bipolar cells are attenuated at an early age. Similar defects are not seen in rd10 mice. Our results indicate that the absence of Tulp1 is associated with a synaptic malformation that precedes photoreceptor degeneration and most likely interferes with the proper development of post-receptoral dendrites. It is evident that Tulp1 plays an important role in photoreceptor synapse development as well as in photoreceptor function and survival.

11.2 Methods

11.2.1 Animals

The generation and genotyping of tulp1–/– mice has been described previously (Hagstrom et al. 1999). Homozygous rd10 breeders (B6.CXB1-Pde6bRD10/J) were