title: Early synaptic defects in tulp1-/- mice.
abstract: OBJECTIVE
  Mutations in the photoreceptor-specific tubby-like protein 1 (TULP1) underlie a form of autosomal recessive retinitis pigmentosa. To investigate the role of Tulp1 in the photoreceptor synapse, the authors examined the presynaptic and postsynaptic architecture and retinal function in tulp1(-/-) mice
  
  
  METHODS
  The authors used immunohistochemistry to examine tulp1(-/-) mice before retinal degeneration and made comparisons with wild-type (wt) littermates and retinal degeneration 10 (rd10) mice, another model of photoreceptor degeneration that has a comparable rate of degeneration. Retinal function was characterized with the use of electroretinography.
  
  
  RESULTS
  In wt mice, Tulp1 is localized to the photoreceptor synapse. 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. Comparable abnormalities are not seen in rd10 mice. The leading edge of the a-wave had normal kinetics in tulp1(-/-) mice but reduced gain in rd10 mice. The b-wave intensity-response functions of tulp1(-/-) mice are shifted to higher intensities than in wt mice, but those of rd10 mice are not.
  
  
  CONCLUSIONS
  Photoreceptor synapses and bipolar cell dendrites in tulp1(-/-) mice display abnormal structure and function. A malformation of the photoreceptor synaptic ribbon is likely the cause of the dystrophy in bipolar cell dendrites. The association of early-onset, severe photoreceptor degeneration preceded by synaptic abnormalities appears to represent a phenotype not previously described. Not only is Tulp1 critical for photoreceptor function and survival, it is essential for the proper development of the photoreceptor synapse.
authors.affiliation: Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Grossman
authors.forename: Gayle J T
authors.initials: GJ
authors.lastname: Pauer
authors.forename: Umadevi
authors.initials: U
authors.lastname: Narendra
authors.forename: Neal S
authors.initials: NS
authors.lastname: Peachey
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Hagstrom
mesh_terms: D000429:Alcohol Oxidoreductases; D000818:Animals; D000831:Animals, Newborn; D056970:Co-Repressor Proteins; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003712:Dendrites / Q000473:pathology*; D004596:Electroretinography; D005136:Eye Proteins / Q000502:physiology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism* / Q000473:pathology; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000473:pathology; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051245:Retinal Bipolar Cells / Q000473:pathology*; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012243:Rhodopsin / Q000378:metabolism; D013572:Synaptic Vesicles / Q000473:pathology*
chemical_list: C498441:Bsn protein, mouse; D056970:Co-Repressor Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C498631:Pclo protein, mouse; D010750:Phosphoproteins; C491353:Tulp1 protein, mouse; D012243:Rhodopsin; D000429:Alcohol Oxidoreductases; C111341:Ctbp2 protein, mouse; D051571:Protein Kinase C-alpha