Oncogene expression in retinal horizontal cells of transgenic mice results in a cascade of neurodegeneration.
The phenylethanolamine N-methyltransferase promoter directs the expression of the SV40 T antigen to subsets of amacrine and horizontal neurons of the retina in a line of transgenic mice. T antigen expression begins in these cells during the first postnatal week. The horizontal cells appear to develop normally for another week but then begin to die. Subsequently, most of the horizontal cells disappear from the central and mid retina, resulting in loss of the outer plexiform layer and absence of ribbon synapses between the photoreceptors and bipolar cells. Neuronal transformation occurs only in the peripheral retina. These experiments indicate that horizontal neurons are heterogeneous with respect to susceptibility to transformation and that T antigen expression in a subset of horizontal neurons can be a direct cause of neuronal cell death. Furthermore, critical interdependencies exist between horizontal neurons after retinal neurogenesis is complete.
CNS Cell and Molecular Neurobiology, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492.
J P
JP
Hammang
R R
RR
Behringer
E E
EE
Baetge
R D
RD
Palmiter
R L
RL
Brinster
A
A
Messing
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression; D007150:Immunohistochemistry; D019868:Kanamycin Kinase; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000502:physiology*; D009857:Oncogenes; D010770:Phosphotransferases / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000096:biosynthesis; D012160:Retina / Q000166:cytology / Q000502:physiology*; D013539:Simian virus 40 / Q000235:genetics; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure
D000952:Antigens, Polyomavirus Transforming; D011993:Recombinant Fusion Proteins; D010770:Phosphotransferases; D019868:Kanamycin Kinase