Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons (original) (raw)

Nature Genetics volume 17, pages 75–78 (1997)Cite this article

Abstract

Angelman syndrome (AS) is a human genetic disorder characterized by mental retardation, seizures, inappropriate laughter, abnormal gait, tremor and ataxia1–3. There is strong genetic evidence that the disorder is associated with a maternally expressed, imprinted gene mapping to chromosome 15q11–13. Affected patients demonstrate varied molecular abnormalities including large maternal deletions, uniparental paternal disomy (UPD), imprinting mutations4 and loss of function mutations of E6–associated-protein (E6-AP) ubiquitin–protein ligase (UBE3A)5,6. All of these abnormalities are associated with loss of maternal expression of UBE3A. Although mutations in UBE3A cause AS, indicating that maternal-specific expression of UBE3A is essential for a normal phenotype, evidence for maternal-specific expression of UBE3A has been lacking7,8. Using mice with partial paternal UPD encompassing Ube3a to differentiate maternal and paternal expression, we found by in situ hybridization that expression of Ube3a in Purkinje cells, hippocampal neurons and mitral cells of the olfactory bulb in UPD mice was markedly reduced compared to non-UPD littermates. In contrast, expression of Ube3a in other regions of the brain was only moderately or not at all reduced in UPD mice. The major phenotypic features of AS correlate with the loss of maternal-specific expression of Ube3a in hippocampus and cerebellum as revealed in the mouse model.

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Authors and Affiliations

  1. Department of Biochemistry, Baylor College of Medicine, Houston, Texas, 77030, USA
    Urs Albrecht & Gregor Eichele
  2. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA
    James S. Sutcliffe & Arthur L. Beaudet
  3. Department of Pathology, Baylor College of Medicine, Houston, Texas, 77030, USA
    Dawna Armstrong
  4. Howard Hughes Medical Institute, Houston, Texas, 77030, USA
    Arthur L. Beaudet
  5. Mammalian Genetics Unit, Medical Research Council, Harwell, Didcot, Oxfordshire, OXI 1 ORD, UK
    Bruce M. Cattanach & Colin V. Beechey

Authors

  1. Urs Albrecht
  2. James S. Sutcliffe
  3. Bruce M. Cattanach
  4. Colin V. Beechey
  5. Dawna Armstrong
  6. Gregor Eichele
  7. Arthur L. Beaudet

Corresponding author

Correspondence toArthur L. Beaudet.

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Albrecht, U., Sutcliffe, J., Cattanach, B. et al. Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons.Nat Genet 17, 75–78 (1997). https://doi.org/10.1038/ng0997-75

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