Fig. 6.
Kras activation restored ERK phosphorylation and retinal morphology in the Six3-Cre; LSL-KrasG12D; Shp2flox/flox compound mutants. (A) As shown by Western blotting, expression of the activated KrasG12D allele in the Six3-Cre; LSL-KrasG12D; Shp2flox/flox mutant restored the phospho-ERK level to that of the wild type and suppressed phospho-Stat3 expression, while phospho-AKT levels remained unchanged. (B to G) The optic nerve morphology and histology was rescued in the Six3-Cre; LSL-KrasG12D; Shp2flox/flox mutant. (H to M) While Shp2 staining remained absent in the Six3-Cre; LSL-KrasG12D; Shp2flox/flox mutant, phospho-ERK expression was restored in the Müller glial cells (arrows). (N to S) The retinal histology in the P21 Six3-Cre; LSL-KrasG12D; Shp2flox/flox mutant was comparable to that of the wild type. Notice the recovery of the optic nerve fiber layer/inner limiting membrane layer (arrows). (T) By cell counts, densities of all cell types recovered to the wild-type levels in the Six3-Cre; LSL-KrasG12D; Shp2flox/flox compound mutants. Bar, 50 μm.