PMID- 29715367
OWN - NLM
STAT- MEDLINE
DCOM- 20190215
LR  - 20190215
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 59
IP  - 6
DP  - 2018 May 1
TI  - Conditional Deletion of AP-2alpha and AP-2beta in the Developing Murine Retina Leads to 
      Altered Amacrine Cell Mosaics and Disrupted Visual Function.
PG  - 2229-2239
LID - 10.1167/iovs.17-23283 [doi]
AB  - PURPOSE: The combined action of the activating protein-2 (AP-2) transcription 
      factors, AP-2alpha and AP-2beta, is important in early retinal development, specifically 
      in the formation of horizontal cells. However, in previous studies, it was not 
      possible to analyze postnatal development and function of additional retinal 
      subtypes. METHODS: We used a double conditional deletion of AP-2alpha and AP-2beta from 
      the retina to further examine the combinatory role of these genes in retinal cell 
      patterning and function in postnatal adult mice as measured by Voronoi domain 
      area and nearest-neighbor distance spatial analyses and ERGs, respectively. 
      RESULTS: Conditional deletion of both AP-2alpha and AP-2beta from the retina resulted in 
      a variety of abnormalities, including the absence of horizontal cells, defects in 
      the photoreceptor ribbons in which synapses failed to form, along with evidence 
      of aberrant amacrine cell arrangement. Although no significant changes in 
      amacrine cell population numbers were observed in the double mutants, significant 
      irregularities in the mosaic patterning of amacrine cells was observed as 
      demonstrated by both Voronoi domain areas and nearest-neighbor distances 
      analyses. These changes were further accompanied by an alteration in the retinal 
      response to light as recorded by ERGs. In particular, in the double-mutant mice 
      lacking AP-2alpha and AP-2beta, the b-wave amplitude, representative of interneuron 
      signal processing, was significantly reduced compared with control littermates. 
      CONCLUSIONS: Together these findings demonstrate the requirement for both AP-2alpha 
      and AP-2beta in proper amacrine mosaic patterning and a normal functional light 
      response in the retina.
FAU - Hicks, Emily Anne
AU  - Hicks EA
AD  - McMaster School of Biomedical Engineering, McMaster University, Hamilton, 
      Ontario, Canada.
FAU - Zaveri, Mizna
AU  - Zaveri M
AD  - Department of Pathology and Molecular Medicine, McMaster University, Hamilton, 
      Ontario, Canada.
FAU - Deschamps, Paula A
AU  - Deschamps PA
AD  - Department of Pathology and Molecular Medicine, McMaster University, Hamilton, 
      Ontario, Canada.
FAU - Noseworthy, Michael D
AU  - Noseworthy MD
AD  - McMaster School of Biomedical Engineering, McMaster University, Hamilton, 
      Ontario, Canada.
AD  - Department of Electrical and Computer Engineering, McMaster University, Hamilton, 
      Ontario, Canada.
AD  - Department of Radiology, McMaster University, Hamilton, Ontario, Canada.
FAU - Ball, Alexander
AU  - Ball A
AD  - Department of Pathology and Molecular Medicine, McMaster University, Hamilton, 
      Ontario, Canada.
FAU - Williams, Trevor
AU  - Williams T
AD  - Department of Craniofacial Biology and Department of Cell and Developmental 
      Biology, University of Colorado Denver, Anschutz Medical Campus, Aurora, 
      Colorado, United States.
FAU - West-Mays, Judith A
AU  - West-Mays JA
AD  - McMaster School of Biomedical Engineering, McMaster University, Hamilton, 
      Ontario, Canada.
AD  - Department of Pathology and Molecular Medicine, McMaster University, Hamilton, 
      Ontario, Canada.
LA  - eng
GR  - R01 DE012728/DE/NIDCR NIH HHS/United States
GR  - R01 EY025789/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Transcription Factor AP-2)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Amacrine Cells/*metabolism/ultrastructure
MH  - Animals
MH  - *Animals, Newborn
MH  - Base Sequence
MH  - Cell Count
MH  - DNA/*genetics
MH  - Electroretinography
MH  - Female
MH  - Fluorescent Antibody Technique, Indirect
MH  - *Gene Expression Regulation, Developmental
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Microscopy, Electron, Transmission
MH  - Models, Animal
MH  - Retina/*metabolism/ultrastructure
MH  - *Sequence Deletion
MH  - Transcription Factor AP-2/biosynthesis/*genetics
PMC - PMC5931233
EDAT- 2018/05/02 06:00
MHDA- 2019/02/16 06:00
PMCR- 2018/05/01
CRDT- 2018/05/02 06:00
PHST- 2018/05/02 06:00 [entrez]
PHST- 2018/05/02 06:00 [pubmed]
PHST- 2019/02/16 06:00 [medline]
PHST- 2018/05/01 00:00 [pmc-release]
AID - 2680657 [pii]
AID - IOVS-17-23283R1 [pii]
AID - 10.1167/iovs.17-23283 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2018 May 1;59(6):2229-2239. doi: 
      10.1167/iovs.17-23283.