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. 2019 Nov 22;31:109–123. doi: 10.1016/j.molmet.2019.11.013

Figure 1.

Figure 1

Severe obesity in mice with specific disruption of BDNF expression from promoter I. (A–B) Strategy for generating mice with specific disruption of BDNF expression from exon 1 (a: Bdnf-e1) or exon 4 (b: Bdnf-e4). The Bdnf gene in the mouse has 9 noncoding exons (exon 1–9, blue rectangles) and one coding exon (exon 10, blue rectangle with coding region noted). Each noncoding exon could be transcribed from its respective promoter and alternatively spliced to exon 10 to translate the same BDNF protein. An eGFP-STOP cassette (eGFP, green rectangle, followed by multiple stop codons, black-shaded rectangle) is inserted after exon 1 to generate Bdnf-e1 mutant mice. In Bdnf-e1−/− mice, the e1 transcript (mutant e1 mRNA) driven by promoter I expresses eGFP but not BDNF protein because of the presence of stop codons. (C) Body weight of WT (blue) and Bdnf-e1−/− (red) male mice from 2 months to 9 months of age. (D) Body length of WT (blue) and Bdnf-e1−/− (red) male mice at the age of 6 months. (E) Body weight of WT (blue) and Bdnf-e4−/− (orange) male mice at 2, 3, and 6.5 months. (F) Body weight change before sexual maturity in WT and Bdnf-e1−/− mice. (G) Photographs of WT and Bdnf-e1−/− mice at 9 months of age. (H) Micro–computed tomography images of bone (white), VWAT (green), BAT (red), and HWAT (blue) in WT and Bdnf-e1−/− mice with pseudo-color. (I) Normalized volume of SWAT, VWAT, BAT, and HWAT with body weight in WT and Bdnf-e1−/− mice. In this and all other figures, data are shown as mean ± SEM; n.s., no significant change; *p < 0.05; **p < 0.01; ***p < 0.001. “n” or the number associated with each column represents the number of animals used. Note that a marked body weight increase was observed in Bdnf-e1−/− mice as early as 3 months.