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Disease Models and Mechanisms

Year: 2009  |  Volume: 2  |  Issue: 7-8  |  Page No.: 412 - 418

Haploinsufficiency of the murine polycomb gene Suz12 results in diverse malformations of the brain and neural tube

X Miro, X Zhou, S Boretius, T Michaelis, C Kubisch, G Alvarez Bolado and P. Gruss


Xavier Miro, Xunlei Zhou, Susann Boretius, Thomas Michaelis, Christian Kubisch, Gonzalo Alvarez-Bolado, and Peter Gruss

Polycomb proteins are epigenetic regulators of gene expression. Human central nervous system (CNS) malformations are congenital defects of the brain and spinal cord. One example of a human CNS malformation is Chiari malformation (CM), which presents as abnormal brainstem growth and cerebellar herniation, sometimes accompanied by spina bifida and cortical defects; it can occur in families. Clinically, CM ranges from an asymptomatic condition to one with incapacitating or lethal symptoms, including neural tube defects and hydrocephalus. However, no genes that are causally involved in any manifestation of CM or similar malformations have been identified. Here, we show that a pathway that involves Zac1 (also known as Plagl1 or Lot1) and controls neuronal proliferation is altered in mice that are heterozygous for the polycomb gene Suz12, resulting in a phenotype that overlaps with some clinical manifestations of the CM spectrum. Suz12 heterozygotes show cerebellar herniation and an enlarged brainstem, accompanied by...

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