1 Glycogen-Branching Enzyme Deficiency Leads to Abnormal Cardiac Development: Novel Insights into Glycogen Storage Disease IV

g.oxfordjournals.org/ D ow nloaded from 2 Glycogen storage disease type IV (GSD-IV) is an autosomal recessive disease caused by a deficiency in glycogen-branching enzyme (GBE1) activity that results in accumulation of amylopectin-like polysaccharide, which presumably leads to osmotic swelling and cell death. This disease is extremely heterogeneous in terms of tissue involvement, age of onset, and clinical manifestation. The most severe fetal form presents as hydrops fetalis; however, its pathogenetic mechanisms are largely unknown. In this study, mice carrying a stop codon mutation (E609X) in the Gbe1 gene were generated using a gene-driven mutagenesis approach. Homozygous mutants (Gbe-/- mice) recapitulated the clinical features of hydrops fetalis and th