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Integration of H-2Z1, a Somatosensory Cortex-Expressed Transgene, Interferes with the Expression of theSatb1andTbc1d5Flanking Genes and Affects the Differentiation of a Subset of Cortical Interneurons

Authors: Narboux-Nême, Nicolas; Goïame, Rosette; Mattei, Marie-Genevieve; Cohen-Tannoudji, Michel; Wassef, Marion;

Integration of H-2Z1, a Somatosensory Cortex-Expressed Transgene, Interferes with the Expression of theSatb1andTbc1d5Flanking Genes and Affects the Differentiation of a Subset of Cortical Interneurons

Abstract

H-2Z1 is an enhancer trap transgenic mouse line in which the lacZ reporter delineates the somatosensory area of the cerebral cortex where it is expressed in a subset of layer IV neurons. In the search of somatosensory specific genes or regulatory sequences, we mapped the H-2Z1 transgene insertion site to chromosome 17, 100 and 460 kb away fromTbc1d5andSatb1flanking genes. We show here that insertion of the H-2Z1 transgene results in three distinct outcomes. First, a genetic background-sensitive expression oflacZin several brain and body structures. While four genes in a 1 Mb region around the insertion are expressed in the barrel cortex, H-2Z1 expression resembles more that of its two direct neighbors. Moreover, H-2Z1 closely reports most of the body and brain expression sites of theSatb1chromatin remodeling gene including tooth buds, thymic epithelium, pontine nuclei, fastigial cerebellar nuclei, and cerebral cortex. Second, the H-2Z1 transgene causes insertional mutagenesis ofTbc1d5andSatb1, leading to a strong decrease in their expressions. Finally, insertion of H-2Z1 affects the differentiation of a subset of cortical GABAergic interneurons, a possible consequence of downregulation of Satb1 expression. Thus, the H-2Z1 “somatosensory” transgene is inserted in the regulatory landscape of two genes highly expressed in the developing somatosensory cortex and reports for a subdomain of their expression profiles. Together, our data suggest that regulation of H-2Z1 expression results from local and remote genetic interactions.

Country
France
Keywords

Cerebral Cortex, Cell Differentiation, Mice, Inbred Strains, Mice, Transgenic, Matrix Attachment Region Binding Proteins, Somatosensory Cortex, Mice, Gene Expression Regulation, Lac Operon, Interneurons, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Animals, GABAergic Neurons

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
10
Average
Average
Average
hybrid