title: A Mutation in Syne2 Causes Early Retinal Defects in Photoreceptors, Secondary Neurons, and Müller Glia.
abstract: OBJECTIVE
  The purpose of this study was to identify the molecular basis and characterize the pathological consequences of a spontaneous mutation named cone photoreceptor function loss 8 (cpfl8) in a mouse model with a significantly reduced cone electroretinography (ERG) response.
  
  
  METHODS
  The chromosomal position for the recessive cpfl8 mutation was determined by DNA pooling and by subsequent genotyping with simple sequence length polymorphic markers in an F2 intercross phenotyped by ERG. Genes within the candidate region of both mutants and controls were directly sequenced and compared. The effects of the mutation were examined in longitudinal studies by light microscopy, marker analysis, transmission electron microscopy, and ERG.
  
  
  RESULTS
  The cpfl8 mutation was mapped to Chromosome 12, and a premature stop codon was identified in the spectrin repeat containing nuclear envelope 2 (Syne2) gene. The reduced cone ERG response was due to a significant reduction in cone photoreceptors. Longitudinal studies of the early postnatal retina indicated that the cone photoreceptors fail to develop properly, rod photoreceptors mislocalize to the inner nuclear layer, and both rods and cones undergo apoptosis prematurely. Moreover, we observed migration defects of secondary neurons and ectopic Müller cell bodies in the outer nuclear layer in early postnatal development.
  
  
  CONCLUSIONS
  SYNE2 is important for normal retinal development. We have determined that not only is photoreceptor nuclear migration affected, but also the positions of Müller glia and secondary neurons are disturbed early in retinal development. The cpfl8 mouse model will serve as an important resource for further examining the role of nuclear scaffolding and migration in the developing retina.
authors.affiliation: The Jackson Laboratory Bar Harbor, Maine, United States.
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Maddox
authors.affiliation: The Jackson Laboratory Bar Harbor, Maine, United States.
authors.forename: Gayle B
authors.initials: GB
authors.lastname: Collin
authors.affiliation: University of Wisconsin-Madison, Department of Medical Genetics, Madison, Wisconsin, United States.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ikeda
authors.affiliation: The Jackson Laboratory Bar Harbor, Maine, United States.
authors.forename: C Herbert
authors.initials: CH
authors.lastname: Pratt
authors.affiliation: University of Wisconsin-Madison, Department of Medical Genetics, Madison, Wisconsin, United States.
authors.forename: Sakae
authors.initials: S
authors.lastname: Ikeda
authors.affiliation: University of Wisconsin-Madison, Department of Medical Genetics, Madison, Wisconsin, United States 3University of Miami, Miller School of Medicine, Miami, Florida, United States.
authors.forename: Britt A
authors.initials: BA
authors.lastname: Johnson
authors.affiliation: The Jackson Laboratory Bar Harbor, Maine, United States.
authors.forename: Ron E
authors.initials: RE
authors.lastname: Hurd
authors.affiliation: The Jackson Laboratory Bar Harbor, Maine, United States.
authors.forename: Lindsay S
authors.initials: LS
authors.lastname: Shopland
authors.affiliation: The Jackson Laboratory Bar Harbor, Maine, United States.
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Naggert
authors.affiliation: The Jackson Laboratory Bar Harbor, Maine, United States.
authors.forename: Bo
authors.initials: B
authors.lastname: Chang
authors.affiliation: The Jackson Laboratory Bar Harbor, Maine, United States.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Krebs
authors.affiliation: The Jackson Laboratory Bar Harbor, Maine, United States.
authors.forename: Patsy M
authors.initials: PM
authors.lastname: Nishina
mesh_terms: D000818:Animals; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009457:Neuroglia / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics*; D010786:Photoreceptor Cells / Q000473:pathology*; D012160:Retina / Q000473:pathology*
chemical_list: D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C485903:Syne2 protein, mouse