An interval of the obesity QTL Nob3.38 within a QTL hotspot on chromosome 1 modulates behavioral phenotypes.

A region on mouse distal chromosome 1 (Chr. 1) that is highly enriched in quantitative trait loci (QTLs) controlling neural and behavioral phenotypes overlaps with the peak region of a major obesity QTL (Nob3.38), which we identified in an intercross of New Zealand Obese (NZO) mice with C57BL/6J (B6...

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Autores principales: Heike Vogel, Dirk Montag, Timo Kanzleiter, Wenke Jonas, Daniela Matzke, Stephan Scherneck, Alexandra Chadt, Jonas Töle, Reinhart Kluge, Hans-Georg Joost, Annette Schürmann
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:31061d27c7fe400aaea0c2d8aba75d5d2021-11-18T08:02:41ZAn interval of the obesity QTL Nob3.38 within a QTL hotspot on chromosome 1 modulates behavioral phenotypes.1932-620310.1371/journal.pone.0053025https://doaj.org/article/31061d27c7fe400aaea0c2d8aba75d5d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23308133/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203A region on mouse distal chromosome 1 (Chr. 1) that is highly enriched in quantitative trait loci (QTLs) controlling neural and behavioral phenotypes overlaps with the peak region of a major obesity QTL (Nob3.38), which we identified in an intercross of New Zealand Obese (NZO) mice with C57BL/6J (B6). By positional cloning we recently identified a microdeletion within this locus causing the disruption of Ifi202b that protects from adiposity by suppressing expression of 11β-Hsd1. Here we show that the Nob3.38 segment also corresponds with the QTL rich region (Qrr1) on Chr. 1 and associates with increased voluntary running wheel activity, Rota-rod performance, decreased grip strength, and anxiety-related traits. The characterization of a subcongenic line carrying 14.2 Mbp of Nob3.38 with a polymorphic region of 4.4 Mbp indicates that the microdeletion and/or other polymorphisms in its proximity alter body weight, voluntary activity, and exploration. Since 27 out of 32 QTL were identified in crosses with B6, we hypothesized that the microdeletion and or adjacent SNPs are unique for B6 mice and responsible for some of the complex Qrr1-mediated effects. Indeed, a phylogenic study of 28 mouse strains revealed a NZO-like genotype for 22 and a B6-like genotype for NZW/LacJ and 4 other C57BL strains. Thus, we suggest that a Nob3.38 interval (173.0-177.4 Mbp) does not only modify adiposity but also neurobehavioral traits by a haplotype segregating with C57BL strains.Heike VogelDirk MontagTimo KanzleiterWenke JonasDaniela MatzkeStephan ScherneckAlexandra ChadtJonas TöleReinhart KlugeHans-Georg JoostAnnette SchürmannPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53025 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Heike Vogel
Dirk Montag
Timo Kanzleiter
Wenke Jonas
Daniela Matzke
Stephan Scherneck
Alexandra Chadt
Jonas Töle
Reinhart Kluge
Hans-Georg Joost
Annette Schürmann
An interval of the obesity QTL Nob3.38 within a QTL hotspot on chromosome 1 modulates behavioral phenotypes.
description A region on mouse distal chromosome 1 (Chr. 1) that is highly enriched in quantitative trait loci (QTLs) controlling neural and behavioral phenotypes overlaps with the peak region of a major obesity QTL (Nob3.38), which we identified in an intercross of New Zealand Obese (NZO) mice with C57BL/6J (B6). By positional cloning we recently identified a microdeletion within this locus causing the disruption of Ifi202b that protects from adiposity by suppressing expression of 11β-Hsd1. Here we show that the Nob3.38 segment also corresponds with the QTL rich region (Qrr1) on Chr. 1 and associates with increased voluntary running wheel activity, Rota-rod performance, decreased grip strength, and anxiety-related traits. The characterization of a subcongenic line carrying 14.2 Mbp of Nob3.38 with a polymorphic region of 4.4 Mbp indicates that the microdeletion and/or other polymorphisms in its proximity alter body weight, voluntary activity, and exploration. Since 27 out of 32 QTL were identified in crosses with B6, we hypothesized that the microdeletion and or adjacent SNPs are unique for B6 mice and responsible for some of the complex Qrr1-mediated effects. Indeed, a phylogenic study of 28 mouse strains revealed a NZO-like genotype for 22 and a B6-like genotype for NZW/LacJ and 4 other C57BL strains. Thus, we suggest that a Nob3.38 interval (173.0-177.4 Mbp) does not only modify adiposity but also neurobehavioral traits by a haplotype segregating with C57BL strains.
format article
author Heike Vogel
Dirk Montag
Timo Kanzleiter
Wenke Jonas
Daniela Matzke
Stephan Scherneck
Alexandra Chadt
Jonas Töle
Reinhart Kluge
Hans-Georg Joost
Annette Schürmann
author_facet Heike Vogel
Dirk Montag
Timo Kanzleiter
Wenke Jonas
Daniela Matzke
Stephan Scherneck
Alexandra Chadt
Jonas Töle
Reinhart Kluge
Hans-Georg Joost
Annette Schürmann
author_sort Heike Vogel
title An interval of the obesity QTL Nob3.38 within a QTL hotspot on chromosome 1 modulates behavioral phenotypes.
title_short An interval of the obesity QTL Nob3.38 within a QTL hotspot on chromosome 1 modulates behavioral phenotypes.
title_full An interval of the obesity QTL Nob3.38 within a QTL hotspot on chromosome 1 modulates behavioral phenotypes.
title_fullStr An interval of the obesity QTL Nob3.38 within a QTL hotspot on chromosome 1 modulates behavioral phenotypes.
title_full_unstemmed An interval of the obesity QTL Nob3.38 within a QTL hotspot on chromosome 1 modulates behavioral phenotypes.
title_sort interval of the obesity qtl nob3.38 within a qtl hotspot on chromosome 1 modulates behavioral phenotypes.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/31061d27c7fe400aaea0c2d8aba75d5d
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