GABAergic neurons regulate lateral ventricular development via transcription factor Pax5

Genesis - Tập 51 Số 4 - Trang 234-245 - 2013
Nobuhisa Ohtsuka1,2,3, Sylvia Badurek4,5,2, Meinrad Busslinger6, Francine M. Beneš1,7,8,3, Liliana Minichiello4,5,7, Uwe Rudolph1,7,9,8
1Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
2N.O. and S.B. are primary authors with equal contributions.
3Program in Structural and Molecular Neuroscience, McLean Hospital, Belmont, Massachusetts
4Centre for Neuroregeneration, University of Edinburgh, EH16 4SB, Edinburgh, Scotland
5European Molecular Biology Laboratory, Monterotondo, Italy
6Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria
7F.M.B., L.M., and U.R. are senior authors with equal contributions.
8Program in Neuroscience, Harvard Medical School, Boston, Massachusetts
9Laboratory of Genetic Neuropharmacology, McLean Hospital, Belmont, Massachusetts

Tóm tắt

Summary

Postmortem studies have revealed a downregulation of the transcription factor Pax5 in GABAergic neurons in bipolar disorder, a neurodevelopmental disorder, raising the question whether Pax5 in GABAergic neurons has a role in normal brain development. In a genetic approach to study functions of Pax5 in GABAergic neurons, Pax5 was specifically deleted in GABAergic neurons from Pax5 floxed mice using a novel Gad1‐Cre transgenic mouse line expressing Cre recombinase in Gad1‐positive, that is, GABAergic neurons. Surprisingly, these mice developed a marked enlargement of the lateral ventricles at approximately 7 weeks of age, which was lethal within 1–2 weeks of its appearance. This hydrocephalus phenotype was observed in mice homozygous or heterozygous for the Pax5 conditional knockout, with a gene dosage‐dependent penetrance. By QTL (quantitative trait loci) mapping, a 3.5 Mb segment on mouse chromosome 4 flanked by markers D4Mit237 and D4Mit214 containing approximately 92 genes including Pax5 has previously been linked to differences in lateral ventricular size. Our findings are consistent with Pax5 being a relevant gene underlying this QTL phenotype and demonstrate that Pax5 in GABAergic neurons is essential for normal ventricular development. genesis 51:234–245. © 2013 Wiley Periodicals, Inc.

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Genesis

Tập 51 Số 4

234-245

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