Anti-ADRA1A polyclonal antibody

Comparative anchor tagged sequence (CATS) consensus primers from loci mapped to human chromosomes 9, 10, 20, and 22 have been used to amplify homologous loci in pigs. Of 53, CATS primers tested in pigs, only 23 yielded products homologous to the human locus (42% success). Ten loci were physically mapped (43% success rate for verified products, but only 19% for primers tested). Due to lack of polymorphism, linkage mapping was possible only for AMBP. Map locations were consistent with human/pig ZOO-FISH, except for ADRA1A, whose position is still equivocal in humans. These CATS primers have made very limited contributions to pig/human comparative gene mapping because of low efficiency of amplification of orthologous porcine product, frequent amplification from rodent template in a somatic hybrid panel and low level of polymorphism.

Cardiomyocytes from human embryonic stem cells (hESC-CMs) and induced pluripotent stem cells (hiPSC-CMs) represent new models for drug discovery. Although hypertrophy is a high-priority target, we found that hiPSC-CMs were systematically unresponsive to hypertrophic signals such as the alpha-adrenoceptor (alpha AR) agonist phenylephrine (PE) compared to hESC-CMs. We investigated signaling at multiple levels to understand the underlying mechanism of this differential responsiveness. The expression of the normal alpha(1)AR gene, ADRA1A, was reversibly silenced during differentiation, accompanied by ADRA1B upregulation in either cell type. ADRA1B signaling was intact in hESC-CMs, but not in hiPSC-CMs. We observed an increased tonic activity of inhibitory kinase pathways in hiPSC-CMs, and inhibition of antihypertrophic kinases revealed hypertrophic increases. There is tonic suppression of cell growth in hiPSC-CMs, but not hESC-CMs, limiting their use in investigation of hypertrophic signaling. These data raise questions regarding the hiPSC-CM as a valid model for certain aspects of cardiac disease.