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Pathological Changes in the Heart of the Strain CUX1 Transgenic Mice
Author(s) -
Fletcher A,
Raza F,
Buursma J,
Livingston S,
Kearn D,
Herndon B,
Vanden Heauvel G,
Baybutt R,
Molteni A
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb432
Subject(s) - fibrosis , medicine , inflammation , pathology , genetically modified mouse , transgene , biology , gene , biochemistry
CUX1 is a transcriptional repressor gene in the network controlling G1‐S phase transition. It represses the expression of the cyclin kinase (CK1) inhibitors p21 and p27. Transgenic mice constitutively expressing CUX1 develop multiorgan damage consequent to aberrant p27 expression in the kidneys (polycystic), testes (diminished spermatogenesis), and liver (fibrosis). These mice also present severe pulmonary inflammation, vasculitis, bronchiolitis, bronchiectasis, and fibrosis. This study relates to the damage induced to the heart consequent to the CUX1 expression. H&E staining of the mice hearts showed extensive myocardial inflammation, interstitial edema, hemorrhages, and increased number of macrophages neutrophils, and lymphocytes. Clusters of myocardial fibers were intensively eosinophilic with nuclear pyknosis and karyolysis suggesting the development of infarctions. A semi‐quantitative evaluation of the histopathological damage made by two pathologists unaware of the slides identity, with damage graded on a scale from 5 (minimal) to 50 (very severe), reported an average value 6.28 + 2.99 for hearts of WTF (controls) vs 22.99 + 3.52 for hearts of CUX1 mice (P< 0.0001). Coronary arteries of the CUX1 mice had a trend indicating medial wall thickening and reduced lumen patency (68% vs 75% of WTF). This data indicates that the damage of the CUX1 mice is also extended to the heart. Additional studies are needed to establish whether such damage is consequent to that of the lungs or originates directly in the organ by p27 effect.