![Figure 1. ATP13A2-null mice develop autophagy impairment-like phenotypes. (a and b) Hepatomegaly of ATP13A2-null mice. Livers of control (WT) and ATP13A2-null (knockout [KO]) mice (a) at age 16–18 mo and quantitative analysis of liver mass related to their body weight (b) are shown. ****, P < 0.0001. WT: n = 17, KO: n = 13. (c) H&E staining of liver tissues. Representative images of liver tissues of control (WT) and ATP13A2 null (KO) mice with H&E stain are shown. PV, portal vein. Upper panel: bar, 200 µm; lower panel: bar, 50 µm. (d and e) Reduced adipose tissue mass. Adipose tissues of control (WT) and ATP13A2-null (KO) mice (d) at age 16–18 mo and quantitative analysis of adipose tissue mass related to their body weight (e) are shown. *, P < 0.05. WT: n = 5, KO: n = 5. (f) H&E staining of adipose tissues. Representative images of adipose tissues of control (WT) and ATP13A2-null (KO) mice with H&E stain are shown. Bar, 200 µm. (g and h) Oil red O and periodic acid–Schiff staining. Representative images of livers of control (WT) and ATP13A2-null (KO) mice with oil red O staining (g) and periodic acid–Schiff staining (h) are shown. PV, portal vein. Bar, 20 µm (g), 200 µm (h). (i–k) Detection of p62 and LC3-II. Liver tissue lysates of control (WT) and ATP13A2-null (KO) mice were immunodetected for p62, LC3 (LC3-II) and α-tubulin (α-tub) (i). Quantitative analysis of p62 (j) and LC3-II (k) is shown. *, P < 0.05, n = 3. (l) Accumulation of ubiquitinated insoluble proteins in ATP13A2-null mice. Triton X-100–soluble (left panel) and –insoluble (right panel) proteins were extracted from livers of control (WT) and ATP13A2-null (KO) mice, followed by immunodetection for ubiquitin (Ubi) and actin. (m and n) TEM analysis of liver tissues of control (WT) and ATP13A2-null (KO) mice. Yellow arrows: APSs; white arrows: multivesicular bodies (MVBs; m). Bar, 1 µm. Higher magnification images are shown (Zoom). Bar, 0.1 µm. (n) Quantitative analysis of APSs and MVBs in relative images (2.5 × 2.5 µm2 per image) is shown. **, P < 0.01; ****, P < 0.0001. WT: n = 36, KO: n = 42.](https://cdn.rupress.org/rup/content_public/journal/jcb/218/1/10.1083_jcb.201804165/25/jcb_201804165_fig1.jpeg?Expires=1767685853&Signature=Pe4bceHqrGxMp6v3fu5HEFTNR2WdAi40vMWhXFnbBUwd4PjnWref3cU4WMlVtwz79Bt4NLBonwuTuEP7UNwhx3iXz3y1msV9b3FJWdRHZNrldi3GIqwJxkTWuOeccFtBR0McFApwH1vSa58tjLrMLTZC5NoFWeAjhPniAA0-K-bWKPDl6F6M-IDYCKNr7qAfpjsGOhrz-D1DA7DBBLvyBdbxc8vDkelHm9Tf3RIdF5puKN3eC0r3ke8vo75GawJaqZQxXRenYY4ajAxwuQYizDDE8p-K4iVwUqyOqDGTLiyElDdIuKreorNdu1VhKVWjvcmc5cVQSgmf2ktn9bfN6A__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
ATP13A2-null mice develop autophagy impairment-like phenotypes. (a and b) Hepatomegaly of ATP13A2-null mice. Livers of control (WT) and ATP13A2-null (knockout [KO]) mice (a) at age 16–18 mo and quantitative analysis of liver mass related to their body weight (b) are shown. ****, P < 0.0001. WT: n = 17, KO: n = 13. (c) H&E staining of liver tissues. Representative images of liver tissues of control (WT) and ATP13A2 null (KO) mice with H&E stain are shown. PV, portal vein. Upper panel: bar, 200 µm; lower panel: bar, 50 µm. (d and e) Reduced adipose tissue mass. Adipose tissues of control (WT) and ATP13A2-null (KO) mice (d) at age 16–18 mo and quantitative analysis of adipose tissue mass related to their body weight (e) are shown. *, P < 0.05. WT: n = 5, KO: n = 5. (f) H&E staining of adipose tissues. Representative images of adipose tissues of control (WT) and ATP13A2-null (KO) mice with H&E stain are shown. Bar, 200 µm. (g and h) Oil red O and periodic acid–Schiff staining. Representative images of livers of control (WT) and ATP13A2-null (KO) mice with oil red O staining (g) and periodic acid–Schiff staining (h) are shown. PV, portal vein. Bar, 20 µm (g), 200 µm (h). (i–k) Detection of p62 and LC3-II. Liver tissue lysates of control (WT) and ATP13A2-null (KO) mice were immunodetected for p62, LC3 (LC3-II) and α-tubulin (α-tub) (i). Quantitative analysis of p62 (j) and LC3-II (k) is shown. *, P < 0.05, n = 3. (l) Accumulation of ubiquitinated insoluble proteins in ATP13A2-null mice. Triton X-100–soluble (left panel) and –insoluble (right panel) proteins were extracted from livers of control (WT) and ATP13A2-null (KO) mice, followed by immunodetection for ubiquitin (Ubi) and actin. (m and n) TEM analysis of liver tissues of control (WT) and ATP13A2-null (KO) mice. Yellow arrows: APSs; white arrows: multivesicular bodies (MVBs; m). Bar, 1 µm. Higher magnification images are shown (Zoom). Bar, 0.1 µm. (n) Quantitative analysis of APSs and MVBs in relative images (2.5 × 2.5 µm2 per image) is shown. **, P < 0.01; ****, P < 0.0001. WT: n = 36, KO: n = 42.
