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Further immunohistochemical characterization of BRD1 a new susceptibility gene for schizophrenia and bipolar affective disorder

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Abstract

We have recently shown that the gene BRD1 is associated with schizophrenia and bipolar affective disorder and that the BRD1 protein (BRD1) which is expressed in neurons may occur in a short and a long variant. The aim of the study was to generate polyclonal antibodies against new BRD1 epitopes enabling discrimination between the long and short BRD1 variants, and elucidate the BRD1 distribution in several human tissues, including the CNS. Polyclonal rabbit antibodies were raised against three different BRD1 epitopes. One (67) was specific for the long BRD1 variant, whereas the two others (63/64 and 65/66) like the original monoclonal mouse antibody (K22) were predicted to stain both variants. Immunohistochemical staining procedures were subsequently performed on paraffin-embedded human cerebral cortex and microarray slides containing 30 different human tissues. Western blotting confirmed the predicted specificity of the developed antibodies. K22, 63/64 and 65/66 displayed a similar neuronal staining pattern characterized by a distinct but weak nuclear staining, while the surrounding cytoplasm and proximal dendrites were more intensely stained. Interestingly, staining with 67 generated in contrast primarily an intense nuclear staining. The new antibodies resulted, furthermore, in a prominent neuroglial reaction characterized by staining of cell bodies, nuclei and glial processes. The tissue microarray analysis revealed that BRD1 was widely distributed in human tissues. The particular expression profile, e.g., the degree of nuclear and/or cytoplasmatic staining, seemed, however, to be highly tissue dependent. These results suggest a general role of BRD1 in the cell and stress that the two BRD1 variants may play different roles in the etiology of psychiatric disease.

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Abbreviations

BRD1:

Bromodomain-containing 1 gene peptide

BRD1 :

Bromodomain-containing 1 gene

BRL :

BR140-like gene, now known as BRD1

BRD1-L :

The long BRD1 splice variant

BRD1-S :

The short BRD1 splice variant

HE:

Hematoxylin and eosin stain

K22:

Original monoclonal mouse antibody directed against BRD1

TBS:

Tris-buffered saline

63/64:

Polyclonal rabbit antibody directed against BRD1

65/66:

Polyclonal rabbit antibody directed against BRD1

67:

Polyclonal rabbit antibody directed against BRD1-L

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Acknowledgments

The authors acknowledge with gratitude the human donors to the Institute of Anatomy and the skillful assistance of Ms. D. Jensen, Mr. A. Meier, Ms. A. Hedemand, Ms. M.M. Hansen & Ms. T. Hindkjær. The Aarhus University Research Foundation, The Danish Medical Research Council, The Foundation for the Advancement of Medical Science, The Lily Benthine Lund Foundation, The Research Foundation of the Danish Medical Association, Pulje til styrkelse af Psykiatrisk Forskning, The Novo Nordic Foundation, The Aase and Ejnar Danielsen Foundation, The Foundation of Direktør Ib Henriksen, The Foundation of Jacob Madsen and Wife, The Foundation of consultant dr. med. E. Geert-Jørgensen and Wife, The Jascha Foundation, and The Foundation of King Christian the 10th financially supported the study.

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Authors and Affiliations

  1. Institute of Anatomy, Faculty of Health Sciences, University of Aarhus, 8000, Århus C, Denmark

    Carsten Reidies Bjarkam

  2. Institute of Human Genetics, University of Aarhus, Århus C, Denmark

    Thomas J. Corydon, Jonatan Pallesen, Mette Nyegaard, Tue Fryland & Anders D. Børglum

  3. Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark

    Inger Marie L. Olsen, Ole Mors & Anders D. Børglum

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  1. Carsten Reidies Bjarkam
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  2. Thomas J. Corydon
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  3. Inger Marie L. Olsen
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  8. Anders D. Børglum
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Correspondence to Carsten Reidies Bjarkam.

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Bjarkam, C.R., Corydon, T.J., Olsen, I.M.L. et al. Further immunohistochemical characterization of BRD1 a new susceptibility gene for schizophrenia and bipolar affective disorder. Brain Struct Funct 214, 37–47 (2009). https://doi.org/10.1007/s00429-009-0219-3

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  • DOI: https://doi.org/10.1007/s00429-009-0219-3

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