Figure 3. Transgenic mice overexpressing the Tgfbr2^G357W mutant allele recapitulate vascular LDS phenotypes.

(A) Schematic representation of control (1x Tg-Tgfbr2) and mutant (1x Tg-Tgfbr2^GW) transgenic constructs, both under the control of the Rosa26 promoter. (B) Expression of endogenous and transgenic cDNA in aortic tissue of 1x Tg-Tgfbr2, 1x Tg-Tgfbr2^GW, and control mice, as evaluated by RT-PCR and indicated underneath the blots. After digestion with the restriction enzyme MfeI, which cuts the transgenic (both control and mutant) but not the endogenous cDNA, the PCR product was incubated with a radioactive probe specific for the Tgfbr2 cDNA (the black lines indicate lanes that were run on the same gel but were noncontiguous). (C) Aortic root diameter of 24-week-old mice, as measured by echocardiography (n ≥ 6). (D) Quantification of elastin fiber breaks per high-power field in control and mutant transgenic mice (n ≥ 6) and representative VVG-stained aortic root sections from 24-week-old wild-type and transgenic mice. (C and D) The upper and lower margins of the box define the 75th and 25th percentiles, respectively; the internal line defines the median, and the whiskers define the range. Scale bar: 40 μm. (E) Representative images of vascular anatomy in control and transgenic mouse models. (F) Kaplan-Meier survival curve showing reduced life span for 2x Tg-Tgfbr2^GW mice but not for 1x Tg-Tgfbr2 and 1x Tg-Tgfbr2^GW mice (wild-type, n = 25; 1x Tg-Tgfbr2, n = 23; 1x Tg-Tgfbr2^GW, n = 26; 2x Tg-Tgfbr2^GW, n = 30). *P < 0.05, ^††P < 0.00005.