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A new mouse line based on the Gpr101 promoter drives expression of Cre in medium spiny neurons of the striatum.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

A novel transgenic mouse that expresses the Cre recombinase in striatal medium spiny neurons was generated. To create the line, we have used the promoter of the X-linked gene Gpr101 and a Bacterial Artificial Chromosome recombineering strategy. When the Gpr101-Cre mouse was bred to the tdTomato Ai14 [1] reporter line, we observed strong fluorescence in medium-size spiny neurons (MSNs) of the striatum. In addition, Gpr101-Cre was detected in hippocampal pyramidal neurons and sparse cerebellar purkinje cells. Interestingly, Gpr101-Cre expression in this mouse line differs from the endogenous Gpr101 gene expression, which is highest in amygdala and hypothalamus and not detected in striatum in adult mice, as shown by in situ hybridization. The tdTomato Ai14 reporter marks any cell lineages in which Gpr101-Cre has, at any time, been expressed. Our results show that the Gpr101-Cre gene construct had lost the original ability of the Gpr101 promotor to drive expression of the Gpr101 gene in the amygdala and the hypothalamus. Second, the Gpr101-Cre gene construct either acquired a novel capability to express in striatum, or more probably, Gpr101 is expressed transiently in striatum during development. In addition, a small subpopulation of astrocytes (GFAP positive cells) was labelled in several regions of the central nervous system, allowing for specific follow-up studies of these cells. We envision that the newly created Cre-line will contribute to numerous studies, particularly related to the development and differentiation of cellular networks in the brain.

URN: urn:nbn:se:uu:diva-156638OAI: oai:DiVA.org:uu-156638DiVA: diva2:432660
Available from: 2011-08-04 Created: 2011-08-04 Last updated: 2012-02-24
In thesis
1. Sexually Dimorphic Gene Expression in the Mammalian Brain
Open this publication in new window or tab >>Sexually Dimorphic Gene Expression in the Mammalian Brain
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In recent times, major advances have been made towards understanding sexual dimorphism in the brain on a molecular basis. This thesis summarises my modest contributions to these endeavours. Sexual dimorphisms are manifested throughout the spectrum of biological complexity, and can be studied by numerous approaches. The approach of this thesis is to explore sex-biased gene expression in mammalian somatic tissues. Paper I describes an evolutionarily conserved sexual gene expression pattern in the primate brain. Conserved sex-biased genes may underlie important sex differences in neurobiology. In Paper II, Y-chromosome genes expressed across several regions of the human male brain during mid-gestation are identified. Such genes may play male-specific roles during brain development. The studies of Papers III and IV explore sex-biased gene expression in several somatic tissues from mouse. The amount of genes with sex-biased expression varied in different brain regions. The striatum was particularly interesting, with an order of magnitude increase in the number of sex-biased genes as compared to the other included brain regions. Of potentially wider significance are my observations regarding the transcriptional regulation of domains that escape X-chromosome inactivation (XCI). Specifically, I provide the first evidence that long non-coding RNAs (lncRNAs) transcribe together with protein-coding genes in XCI-escaping domains. This raises the possibility that lncRNAs mediate the transcriptional regulation of XCI-escaping domains. I also present evidence that the mouse X-chromosome has undergone both feminisation and de-masculinisation during evolution, as indicated by the sex-skewed regulation of genes on this chromosome. This finding is relevant for understanding the selective forces that shaped the mammalian X-chromosome. In the final chapter, Paper V, the generation of a novel transgenic mouse line, Gpr101-Cre, is described. Its progeny can be used for functional studies of striatum, a brain structure with major sexual dimorphism, as is further demonstrated in the Papers of this thesis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 57 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 840
National Category
Developmental Biology
urn:nbn:se:uu:diva-156640 (URN)978-91-554-8118-6 (ISBN)
Public defence
2011-09-16, Zootissalen (EBC 01.01006), Evolutionsbiologiskt centrum, EBC, Norbyvägen, Uppsala, 10:15 (English)
Available from: 2011-08-26 Created: 2011-08-04 Last updated: 2011-11-10

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