Article
Extended Data Fig. 10 | TFEB is constitutively nuclear and active in FLCN-
knockout kidneys, and its depletion rescues mTORC1 hyperactivation.
a, Representative images from three independent histopathological analyses
of FLCN-knockout kidney tissues showing magnifications of areas with tubular
papillary atypical hyperplasia (arrowheads, top), hyperplasia with
considerable alterations of the tubular morphology (marked by asterisks in the
bottom left panel) and atypical hyperplasia with multiple mitoses (represented
in boxed areas and magnified in indents in bottom right panel). Scale bar,
100 μm. b, Representative immunof luorescence analysis of triplicate
experiments of TFEB in kidney sections from mice of the indicated genotypes.
Insets show higher magnification of the boxed area. Scale bars, 100 μm.
c, Immunoblotting analysis of the indicated proteins in cytosolic and nuclear
fractions of kidneys from Flcnflox/flox (Ctrl) and Flcnflox/flox;Ksp-cre+ (Flcn-KO) mice
(replicated three times). d, Immunoblotting analysis of the indicated proteins
in kidneys from Flcnflox/flox;Ksp-cre+ (Flcn-KO) mice and Flcnflox/flox;Tfe bflox/flox;
Ksp-cre+ (Flcn-Tfeb-DKO) mice and corresponding controls (replicated three
times). e, mRNA levels of several TFEB target genes were analysed in kidney
samples from FLCN-knockout mice relative to control mice. Bars represent
mean ± s.e.m. for n = 5 mice for each group and are expressed as fold change
compared with control mice, normalized to cyclophilin gene expression.
*P < 0.05, **P < 0.01, ***P < 0.001, two-sided Student t-test. S16 expression is
shown as a control, unrelated gene. f, Immunohistochemical analysis of LAMP1
in kidney sections from FLCN-knockout mice and control mice (replicated
three times). Insets show higher magnification of the boxed area. Scale bars,
50 μm. In a–f, analysis was performed on 21-day-old mice.