Characterizing Aortic Pathogenesis in Mice

Procedures for handling mice were approved by the Washington University and Sanford-Burnham institutional animal care and use committees. LDLR^−/−B6.129S7-Ldlrtm1Her/J (19 (link)) and SM22-CreTg(Tagln-cre)1Her/J (15 (link)) mice were obtained from The Jackson Laboratory. Msx1(fl/fl);Msx2(fl/fl) mice have been described (20 (link)) and were bred onto the LDLR^−/− background. Experimental SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR^−/−, SM22-Cre;Msx2(fl/fl);LDLR^−/−, and Msx1(fl/fl);Msx2(fl/fl);LDLR^−/− control animals were obtained through the breeding scheme outlined in Fig. 1. At 5–10 weeks of age, animals were weighed. Male sibling cohorts (n = 4–13 per genotype as indicated) of Msx1(fl/fl);Msx2(fl/fl);LDLR^−/− and SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR^−/− mice with equivalent starting weights were challenged with high-fat western diet (HFD) (TD88137; Teklad Lab Animal Diets; Harlan) for 2 months. At the end of the dietary challenge, thoracic aortas were harvested, weighed, and extracted for calcium, collagen, or total RNA, implementing methods previously detailed (9 (link),21 (link)).

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Cheng S.L., Behrmann A., Shao J.S., Ramachandran B., Krchma K., Bello Arredondo Y., Kovacs A., Mead M., Maxson R, & Towler D.A. (2014). Targeted Reduction of Vascular Msx1 and Msx2 Mitigates Arteriosclerotic Calcification and Aortic Stiffness in LDLR-Deficient Mice Fed Diabetogenic Diets. Diabetes, 63(12), 4326-4337.

Publication 2014

LDLR−/−B6.129S7-Ldlrtm1Her/J

Animal Calcium Collagen Dietary Genotype High fat diet Institutional animal care and use committees Ldlr Male Mice Thoracic aortas

Corresponding Organization :

Other organizations : Sanford Burnham Prebys Medical Discovery Institute, The University of Texas MD Anderson Cancer Center, Washington University in St. Louis, University of Southern California, USC Norris Comprehensive Cancer Center, Translational Research Institute for Metabolism and Diabetes

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Variable analysis

independent variables

Genetic manipulation: Experimental genotypes - SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR-/-, SM22-Cre;Msx2(fl/fl);LDLR-/-, Msx1(fl/fl);Msx2(fl/fl);LDLR-/- (control)
Diet: High-fat western diet (HFD)

dependent variables

Thoracic aorta weight
Thoracic aorta calcium content
Thoracic aorta collagen content
Thoracic aorta total RNA

control variables

Age of animals: 5-10 weeks
Sex of animals: Male sibling cohorts
Starting weight of animals: Equivalent

controls

Positive control: Msx1(fl/fl);Msx2(fl/fl);LDLR-/- mice
Negative control: Not explicitly mentioned

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