Fulltext

Mice trisomic for a bacterial artificial chromosome with the single-minded 2 gene (Sim2) show phenotypes similar to some of those present in the partial trisomy 16 mouse models of Down syndrome

Chrast, Roman ; Scott, Hamish S. ; Madani, Rime ; Huber, Lars ; Wolfer, David P. ; Prinz, Marco ; Aguzzi, Adriano ; Lipp, Hans-Peter ; Antonarakis, Stylianos E.

In: Human Molecular Genetics, 2000, vol. 9, no. 12, p. 1853-1864

Ajouter à la liste personnelle
    Titre
    • Mice trisomic for a bacterial artificial chromosome with the single-minded 2 gene (Sim2) show phenotypes similar to some of those present in the partial trisomy 16 mouse models of Down syndrome
    Auteur
    • Chrast, Roman. Division of Medical Genetics, Geneva University Medical School and University Hospital, 1 Rue Michel-Servet, CH-1211 Genève 4, Switzerland, Graduate Program of Cellular and Molecular Biology, Geneva University Medical School, Geneva, Switzerland, Institute of Anatomy, University of Zurich, Zurich, Switzerland and Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    • Scott, Hamish S.. Division of Medical Genetics, Geneva University Medical School and University Hospital, 1 Rue Michel-Servet, CH-1211 Genève 4, Switzerland, Graduate Program of Cellular and Molecular Biology, Geneva University Medical School, Geneva, Switzerland, Institute of Anatomy, University of Zurich, Zurich, Switzerland and Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    • Madani, Rime. Division of Medical Genetics, Geneva University Medical School and University Hospital, 1 Rue Michel-Servet, CH-1211 Genève 4, Switzerland, Graduate Program of Cellular and Molecular Biology, Geneva University Medical School, Geneva, Switzerland, Institute of Anatomy, University of Zurich, Zurich, Switzerland and Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    • Huber, Lars. Division of Medical Genetics, Geneva University Medical School and University Hospital, 1 Rue Michel-Servet, CH-1211 Genève 4, Switzerland, Graduate Program of Cellular and Molecular Biology, Geneva University Medical School, Geneva, Switzerland, Institute of Anatomy, University of Zurich, Zurich, Switzerland and Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    • Wolfer, David P.. Division of Medical Genetics, Geneva University Medical School and University Hospital, 1 Rue Michel-Servet, CH-1211 Genève 4, Switzerland, Graduate Program of Cellular and Molecular Biology, Geneva University Medical School, Geneva, Switzerland, Institute of Anatomy, University of Zurich, Zurich, Switzerland and Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    • Prinz, Marco. Division of Medical Genetics, Geneva University Medical School and University Hospital, 1 Rue Michel-Servet, CH-1211 Genève 4, Switzerland, Graduate Program of Cellular and Molecular Biology, Geneva University Medical School, Geneva, Switzerland, Institute of Anatomy, University of Zurich, Zurich, Switzerland and Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    • Aguzzi, Adriano. Division of Medical Genetics, Geneva University Medical School and University Hospital, 1 Rue Michel-Servet, CH-1211 Genève 4, Switzerland, Graduate Program of Cellular and Molecular Biology, Geneva University Medical School, Geneva, Switzerland, Institute of Anatomy, University of Zurich, Zurich, Switzerland and Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    • Lipp, Hans-Peter. Division of Medical Genetics, Geneva University Medical School and University Hospital, 1 Rue Michel-Servet, CH-1211 Genève 4, Switzerland, Graduate Program of Cellular and Molecular Biology, Geneva University Medical School, Geneva, Switzerland, Institute of Anatomy, University of Zurich, Zurich, Switzerland and Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    • Antonarakis, Stylianos E.. Division of Medical Genetics, Geneva University Medical School and University Hospital, 1 Rue Michel-Servet, CH-1211 Genève 4, Switzerland, Graduate Program of Cellular and Molecular Biology, Geneva University Medical School, Geneva, Switzerland, Institute of Anatomy, University of Zurich, Zurich, Switzerland and Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Human Molecular Genetics, 2000, vol. 9, no. 12, p. 1853-1864. Oxford University Press
    Autre version électronique
    Classification
    • Santé
    Identifiant OAI-PMH
    • oai:doc.rero.ch:304113
    Summary
    The Drosophila single-minded (sim) transcription factor, is a master regulator of fruitfly neurogenesis. Recently, we have cloned and mapped a human homolog of sim, SIM2, to chromosome 21 in the so-called ‘Down syndrome chromosomal region'. Three copies of SIM2 may contribute to some Down syndrome (DS) phenotypes because of the mapping position function as transcriptional repressor, temporal and spatial expression pattern of mouse Sim2, and the potentially analogous role of human SIM2 to that of Drosophila sim during neurogenesis. In order to validate this hypothesis in vivo, we have created the first bacterial artificial chromosome transgenic mice overexpressing a gene possibly involved in DS with only one or two additional copies of mouse Sim2. The transgene was shown to be expressed in the same spatial pattern as the endo­genous gene. The mice develop normally, are fertile and do not show detectable histopathological abnormalities. However, detailed analysis of their behavior revealed anxiety-related/reduced exploratory behaviour and sensitivity to pain, phenotypes similar to those also present in other partial trisomy 16 mouse models of DS. Our data therefore suggest that overexpression of SIM2 contributes to some of the complex DS phenotypes