Newly developed TGF-ß2 knock down transgenic mouse lines express TGF-ß2 differently and its distribution in multiple tissues varies.

BACKGROUND: Transforming growth factor-betas (TGF-ßs), including beta2 (TGF-ß2), constitute a superfamily of multifunctional cytokines with important implications in morphogenesis, cell differentiation and tissue remodeling. TGF-ß2 is thought to play important roles in multiple developmental processes and neuron survival. However, before we carried out these investigations, a TGF-ß2 gene down-regulated transgenic animal model was needed. In the present study, expressional silencing TGF-ß2 was achieved by select predesigning interference short hairpin RNAs (shRNAs) targeting mouse TGF-ß2 genes. RESULTS: Four homozygous transgenic offspring were generated by genetic manipulation and the protein expressions of TGF-ß2 were detected in different tissues of these mice. The transgenic mice were designated as Founder 66, Founder 16, Founder 53 and Founder 41. The rates of TGF-ß2 down-expression in different transgenic mice were evaluated. The present study showed that different TGF-ß2 expressions were detected in multiple tissues and protein levels of TGF-ß2 decreased at different rates relative to that of wild type mice. The expressions of TGF-ß2 proteins in transgenic mice (Founder 66) reduced most by 52%. CONCLUSIONS: The present study generated transgenic mice with TGF-ß2 down-regulated, which established mice model for systemic exploring the possible roles of TGF-ß2 in vivo in different pathology conditions.

Ginsenoside-Rb1 and tetramethylpyrazine phosphate act synergistically to prevent dilated cardiomyopathy in cTnTR141W transgenic mice.

Ginsenoside-Rb1 (Rb1) is known to be partially associated with the inhibition of heparin-binding epidermal growth factor-like growth factor (HB-EGF). Tetramethylpyrazine phosphate (TMPP) inhibits the activation of the calcium/calmodulin/calmodulin-dependent protein kinase (Ca²âº/CaM/CaMKII) pathway. The α-myosin heavy chain cTnT(R141W) transgenic mouse was previously reported as a model for dilated cardiomyopathy (DCM), and it was used to test the effects of combinations of Rb1 and TMPP in reversing the progression of DCM and the potential mechanism. Survival, echocardiography, histologic features assessed the effectiveness of Rb1 and TMPP treatments. Western blot and reverse transcription polymerase chain reactions were used to determine expression levels of certain genes. This study clearly demonstrated that treatment with a combination of Rb1 and TMPP could inhibit the expression of HB-EGF, calmodulin1 (Calm1), and calcium/calmodulin-dependent protein kinase II beta (Camk2b). Rb1 alone mainly reduced the expression of HB-EGF, and TMPP alone mainly reduced the expression of Calm1 and Camk2b. Treatment with Rb1 and TMPP had synergistic effects on the amelioration of chamber dilation, contractile dysfunction, interstitial fibrosis, and ultrastructural degeneration in cTnT(R141W) mice when compared with the results of treatment with Rb1 or TMPP alone, and those were probably due to the inhibition of both HB-EGF and the Ca²âº/CaM/CaMKII pathway.