![]() ![]() ( D) Quantification of Glut1 and Glut4 mRNA levels in muscle (6 weeks, N=4). Data are fold gene expression normalized with cyclophilin and expressed as mean ± S.E.M. ( C) Quantification of TBC1D11 mRNA levels in white adipose tissue. ( B) Western blot showing protein level of Tbc1d1 in non-transgenic and A315T line 23 and line 61 mice. ![]() ( A) Quantification of TBC1D1 mRNA levels in muscle (6 weeks, N=4). Tbc1d1 and Glut4 levels in skeletal muscle and white adipose tissue. ( L) Glucose tolerance test in non-transgenic and A315T line 61 mice (N=5-12). ( G- K) Fasting blood values for glucose ( G), cholesterol ( H), triglycerides ( I), gamma glutamyltransferase ( J), and creatine kinase ( K) in non-transgenic and A315T line 61 mice (8-16 weeks, N= 4-9). ( F) Energy expenditure normalized to lean mass (10 weeks of age N=6 each group). ( E) Food intake normalized to weight for A315T line 61 and non-transgenic controls for a 96 hour period. ( A– D) Cumulative values from individual mice over 96 hours for horizontal X/Y activity ( A and B), vertical Z activity ( C) and food intake ( D) from non-transgenic and A315T line 61 mice in metabolic cages. Metabolic analysis of A315T line 61 mice. Representative western blots are shown, each sample was run ≥ 2 times with N≥ 2 mice in each group analyzed. Tubulin, actin or GAPDH were used as loading controls. 1 µg of total protein loaded per lane for muscle western blot. 10 µg of total protein loaded per lane for WAT western blot. 5 µg of total protein loaded per lane for spinal cord and muscle western blot. Magnification: 400X for immunoflorescence,200X for H&E. ( G) TDP-43 immunoflorescence and H&E stained sections of skeletal muscle of non-transgenic and A315T line 61 (16 weeks of age). ( F) TDP-43 protein levels in skeletal muscle of non-transgenic, A315T line 23, A315T line 61 mice (12 weeks of age) using polyclonal antibody. ( E) Quantification of TDP-43 endogenous and transgene mRNA levels in skeletal muscle (6 weeks, N=4). ( D) TDP-43 protein levels in spinal cord from non-transgenic, A315T line 23 and A315T line 61(12 week old) mice using monoclonal antibody which recognizes human TDP-43 only. A315T line 23 (6 weeks) and A315T line 61 mice (16 weeks). ( C) TDP-43 immuno-reactivity in WAT and BAT of non-transgenic (16 weeks). ( B) TDP-43 protein levels in WAT from 6 week old mice probed with polyclonal antibody that recognizes both human and mouse TDP-43. ( A) Quantification of TDP-43 endogenous and transgene mRNA levels in WAT (6 weeks, N=4). White adipose tissue and muscle in A315T line 23 and line 61 have increased TDP-43 levels. Statistical significance between non-transgenic and A315T mice or between indicated conditions: *P<0.05. ( O) Quantification of white adipocyte size in non-transgenic and A315T line 23 (6 weeks). ( N) H&E of non-transgenic and A315T line 23 mice (6 weeks of age) in WAT. ( J– M) Body composition analysis as measured by Echo MRI for A315T Line 23 and non-transgenic mice, percent fat ( J), total fat ( K), percent lean body composition ( L), and total lean grams ( M). ( I) Weekly weights of TDP-43 A315T Line 23 and non-transgenic mice. ( H) Quantification of white adipocyte size in non-transgenic and A315T line 61 (16 weeks). Magnification: 200X (WAT) and 400X (BAT). ( G) H&E of non-transgenic and A315T line 61 mice (16 weeks) in both WAT and BAT. ( F) Fat pad deposition at 16 weeks in non-transgenic and A315T line 61. ( D– E) Body composition analysis as measured by Echo MRI at 5, 7, 9, and 24-30 weeks for A315T line 61 and non-transgenic mice (N ≥3). ( C) Weight curves of A315T line 61 and non-transgenic mice (N ≥ 4). ( A and B) Increased size in A315T line 61 mice compared to non-transgenic littermates at 10 weeks ( A) and 28 weeks ( B). A315T TDP-43 mice develop marked obesity with a concomitant increase in adipose and decrease in lean mass percentage. ![]()
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