Fig. 5.

Abcc6 deficiency contributes to cardiac fibrosis following treatment with the β-adrenergic agonist, isoproterenol. A: Shows either wild-type C57BL/6J mice or C57BL/6J mice homozygous for a null (gene targeted) allele of Abcc6 (Abcc6^−/−) following treatment with isoproterenol for 3 weeks. Neither strain developed significant calcification (stained with Alizarin Red) but the Abcc6^−/− developed substantially increased fibrosis (stained blue with Masson’s trichrome). B: C3H/HeJ mice are naturally deficient in Abcc6 due to naturally occurring splicing mutation and when treated with isoproterenol develop extensive fibrosis and calcification in the heart. In contrast, C3H/HeJ mice carrying one copy of a genomic Abcc6 clone as a transgene (C3H/HeJ Abcc6^−/−) were resistant to both fibrosis and calcification. Reproduced from (23), with permission.