Differential expression pattern of ZAC in developing mouse and human pancreas

ZAC is a transcription factor and cofactor, a strong candidate for transient neonatal diabetes mellitus (TNDM). TNDM involves impaired beta-cell development and is probably due to a double dose of ZAC , which is normally expressed only from the paternal copy. ZAC and Zac1 (its mouse orthologue) are strongly expressed in the proliferating progenitor/stem cells in many systems and also in some differentiated sites in human and mouse, suggesting a dual role in cell proliferation and differentiation control. Little is known about its expression in developing pancreas, the organ affected in TNDM. In this study, we examined ZAC/Zac1 expression in developing mouse and human pancreas by real-time PCR and dual in situ hybridization and immunofluorescence. Overall pancreatic expression drastically declined during gestation and early post-natal life in the mouse, and between the second trimester and adult in the human. Zac1 was predominantly expressed in mesenchyme in the mouse embryo, while ZAC was specifically expressed in islets of the human fetus. Thus, ZAC/Zac1 may play different roles in mouse and human pancreas development. The specific expression of ZAC in the human fetal beta-cells supports it as the gene involved in TNDM and the different expression pattern of Zac1 in mice from human may explain the much milder phenotype in the mouse model of ZAC double dose.