Homozygous and Heterozygous Reeler Mouse Mutants

  • Patricia Tueting
  • Graziano Pinna
  • Erminio Costa

Reelin is a large-molecular-weight protein secreted during early embryonic development into the extracellular matrix by Cajal-Retzius cells, a temporary population of GABAergic neurons located in the uppermost layer of the developing cortex (marginal zone). In the adult, reelin is exclusively located in GABAergic interneurons of the upper layers of the cortex, and following secretion into the extracellular matrix, surrounds dendritic spines of pyramidal cells located in every layer (Costa et al., 2002). Glutamic acid decarboxylase 67 (GAD67)-positive interneurons of Layer I also exclusively contain DNA methyltransferase 1 (DNMT1) (Ruzicka et al., 2007).

The RELN gene, located on human chromosome 7q22, encodes a 3460-amino-acid protein that is 94% identical to the mouse protein. The promoter region of RELN is rich in CpG islands and, therefore, prone to DNA methylation which results in transcription downregulation of reelin (Chen et al., 2002). Significantly, GABAergic neurons of postmortem brains of schizophrenia and bipolar disorder patients with psychosis are characterized by both reelin downregulation and DNMT1 upregulation (Veldic et al., 2004, 2005). These findings suggest the possibility that reelin promoter methylation by DNMT1 is involved in the dendritic spine hypoplasticity and GABAergic tone downregulation operative in schizophrenia (Costa et al., 2001).


GABAergic Neuron Prepulse Inhibition GABAergic Interneuron Purkinje Cell Loss Reeler Mouse 
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Copyright information

© Springer 2008

Authors and Affiliations

  • Patricia Tueting
    • 1
  • Graziano Pinna
    • 1
  • Erminio Costa
    • 1
  1. 1.Psychiatric Institute/Department of PsychiatryUniversity of Illinois at ChicagoChicago

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