Figure 7
- ID
- ZDB-FIG-230123-26
- Publication
- Sabharwal et al., 2022 - Genetic therapy in a mitochondrial disease model suggests a critical role for liver dysfunction in mortality
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The liver plays an important role in the pathology of LSFC and genetic liver-specific rescue rescues the lipid defect and mortality in lrpprc homozygous mutant larvae. (A) Representative images of the livers of 6 dpf old lrpprcGBT0235/+and lrpprcGBT0235/GBT0235 mutants at 40× (scale bar: 50 µm). (B) Brightfield image of 6 dpf lrpprc+/+ and lrpprcGBT0235/GBT0235 mutants. Homozygous mutants display a dark liver phenotype as compared to the wild-type controls. The region showing dark liver has been marked by an asterisk (scale bar: 150 µm). (C) Oil red O staining for assessment of lipid accumulation in the 6 dpf mutants and rescued larvae. Increased lipid accumulation was observed in the homozygous mutants compared to wild-type larvae. In the liver-specific rescued homozygous lrpprc mutants, Tg(fabp10:Cre)lrpprcGBT0235/GBT0235, no accumulation of lipids was observed (scale bar: 200 µm). (D) The graph show increase in the relative area of the oil red stain for the accumulated lipids, between wild-types (non-rescued wild-type, lrpprc+/+ and liver-specific rescued wild-type Tg(fabp10:Cre)lrpprc+/+) and lrpprcGBT0235/GBT0235 mutants, indicating an increase in the lipid content (p-value = 0.0083). The levels are restored in homozygous rescued larvae, Tg(fabp10:Cre)lrpprcGBT0235/GBT0235 (p-value < 0.0001). There was no significant difference between wild-types (non-rescued wild-type, lrpprc+/+ and liver-specific rescued wild-type Tg(fabp10:Cre)lrpprc+/+) and liver-specific rescued mutants, Tg(fabp10:Cre)lrpprcGBT0235/GBT0235 (p-value = 0.0623). p-Values were determined by the Mann-Whitney test. Each data point represents a single embryo. For, lrpprc+/+ N = 8; Tg(fabp10:Cre)lrpprc+/+ N = 7; lrpprcGBT0235/GBT0235 N=13; Tg(fabp10:Cre)lrpprcGBT0235/GBT0235, N=10. (Figure 7—source data 1) (E) Liver-specific rescued mutants display an improved survival rate beyond 11 dpf (Figure 7—source data 1). (F) Representative electron micrographs of the mitochondria in hepatocytes for 8 dpf lrpprc wild type, lrpprc homozygous mutants, and liver-specific lrpprc rescued larvae. Altered mitochondrial morphology displayed by lrpprcGBT0235/GBT0235 was observed to be improved in the rescued mutants, Tg(fabp10:Cre)lrpprcGBT0235/GBT0235 (scale bar: 0.5 µm). |