Fig. 1. TgAlk3^QD mice exhibit medullary cystic renal dysplasia and aberrant Myc expression. (A) Histological phenotype and Myc expression. Histological analysis of 4 µm Hematoxylin and Eosin-stained kidney tissue sections. Upper and middle panels: the renal medulla of wild-type mice is characterized by a high density of closely apposed tubules without intervening extracellular matrix. By contrast, the renal medulla of TgAlk3^QD mice is characterized by a heterogeneous population of tubules of irregular shape and variable diameter. Cysts (C) with greatly increased diameter and flattened epithelium are contrasted with normal tubules (T). Lower panels: Myc was detected using an anti-Myc antibody. Although Myc was barely detected in wild-type kidney, it was widely expressed in a nuclear pattern in dysplastic renal tubules. (B) Association of acetyl histone 4 (H4) with the RNA polymerase II core promoter using ChIP. The location and characteristics of the RNA polymerase II core promoter including the TATA box and TFII recognition elements (BRE) in the murine Myc gene are shown in schematic form. Left lower panel: ChIP using an anti-acetyl-histone 4 (H4) and kidney tissue isolated from wild-type or TgAlk3^QD kidney tissue demonstrated increased amplification of the 103 nucleotide core promoter region in dysplastic (QD) tissue. Lower right panel: quantitation of DNA amplified after ChIP, demonstrating a 1.6-fold increase in acetyl-H4 association with the core promoter amplified from TgAlk3^QD tissue. The amount of DNA amplified was controlled for the amount of input DNA. P<0.05, n=3 independent experiments.