Advancing congenital defect phenotyping using HREM imaging

Knockout mouse lines that show embryonic and perinatal lethality are valuable models to investigate the genetic pathways that are associated with human congenital diseases. To elucidate the relationship between a specific gene and a developmental defect, detailed screening of knockout phenotypes is pivotal. Here, Wolfgang Weninger and colleagues used high-resolution episcopic microscopy (HREM) to screen the morphological phenotypes of embryonic day 14.5 (E14.5) embryos of 34 mouse strains that produce prenatally lethal offspring. The authors developed a reliable and ergonomic screening protocol to efficiently and comprehensively score structural abnormalities in those embryos. Their approach enabled them to detect a total of 58 defects that might be missed by employing alternative three-dimensional imaging methods and scoring systems. Many of these defects might be causal to embryonic or perinatal mortality. The results demonstrate that HREM combined with a systematic screening protocol enables more efficient phenotyping of E14.5 mouse embryos than any alternative approach. Such a method will contribute to advancing our knowledge of normal tissue and organ development, and of the causality of congenital diseases. Page 1143