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Blood, Vol. 113, Issue 3, 696-704, January 15, 2009

Genetic elimination of prothrombin in adult mice is not compatible with survival and results in spontaneous hemorrhagic events in both heart and brain
Blood Mullins et al.
113: 696
Supplemental materials for: Mullins et al
Files in this Data Supplement:
- Figure S1. Modest cardiac fibrosis in one-year-old Mx−fIIlox/−mice with low plasma prothrombin (JPG, 91.3 KB)
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Representative low-magnification views of hematoxylin/eosin-stained heart sections prepared from one-year-old wild-type (A) and Mx−fIIlox/− (B) male animals. Although unchallenged young adult Mx−fIIlox/− mice were essentially devoid of any appreciable heart pathology (see main text), well-organized, but generally modest, fibrotic lesions were appreciable in unchallenged year-old Mx−fIIlox/− mice. (C) Low-magnification view of heart section from an exceptional one-year-old Mx−fIIlox/− male with more advanced fibrotic lesions. Representative high-powered views of a heart sections from wild-type (D) and Mx−fIIlox/− (E) animals at one year of age. Note that the fibrotic region in Mx−fIIlox/− mice were organized with fibroblast-like cells. (F) A Mx−fIIlox/− animal with a larger fibrotic lesion. Arrowheads highlight areas of fibrosis. All size bars indicate 100 µm.

- Figure S2. Collagen deposition within the hearts of aged mice with low plasma prothrombin (JPG, 95 KB)
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Representative low-magnification views of Mason’s trichrome-stained stain heart sections from one-year-old wild-type (A) and Mx−fIIlox/− (B) male animals. Collagen (staining blue) was generally diffuse in myocardial tissue of control mice (A), whereas modest focal collagen deposition (arrowheads) was appreciable in aged Mx−fIIlox/− animals (B). Collagen deposition appeared to be qualitatively more prominent in Mx−fIIlox/− males than females (data not shown). (C) Low-powered view of heart section from a Mx−fIIlox/− animal with more prominent collagen deposition at one year of age. (D) Sub-pericardial fibrosis in a one-year-old male with severe fibrotic lesions. Representative high-powered views of heart tissue sections from one-year-old wild-type (E) and Mx−fIIlox/− (F) males. (G) Example of a more severe fibrotic region in a Mx−fIIlox/− male. (H) High-powered view of sub-pericardial collagen deposition in a Mx−fIIlox/− animal. Double arrowheads highlight sub-pericardial fibrotic lesions. All size bars indicate 100 µm.

- Figure 3. Hemosiderin deposition within heart tissue of aged Mx−fIIlox/− mice (JPG, 143 KB)
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Prussian blue-stained heart sections prepared from one-year-old wild-type (A) and Mx−fIIlox/− (B–D) male mice. Note that no evidence of hemosiderin is appreciable in older control animals (A), whereas focal iron deposits (punctuate, dark blue) could be appreciated in both myocardial (B and C) sub-pericardial areas (D) (arrows). (C) High-powered view heart section from a Mx−fIIlox/− male showing juxtaposition of fibrosis and (asterisk) and hemosiderin (arrow). All size bars indicate 100 µm.

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