UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Hypomorphic mutation of the mouse Huntington's disease gene orthologue

Murthy, V; Tebaldi, T; Yoshida, T; Erdin, S; Calzonetti, T; Vijayvargia, R; Tripathi, T; ... Biagioli, M; + view all (2019) Hypomorphic mutation of the mouse Huntington's disease gene orthologue. PLOS Genetics , 15 (3) , Article e1007765. 10.1371/journal.pgen.1007765. Green open access

[thumbnail of pgen.1007765.pdf]
Preview
Text
pgen.1007765.pdf - Published Version

Download (5MB) | Preview

Abstract

Rare individuals with inactivating mutations in the Huntington’s disease gene (HTT) exhibit variable abnormalities that imply essential HTT roles during organ development. Here we report phenotypes produced when increasingly severe hypomorphic mutations in the murine HTT orthologue Htt, (HdhneoQ20, HdhneoQ50, HdhneoQ111), were placed over a null allele (Hdhex4/5). The most severe hypomorphic allele failed to rescue null lethality at gastrulation, while the intermediate, though still severe, alleles yielded recessive perinatal lethality and a variety of fetal abnormalities affecting body size, skin, skeletal and ear formation, and transient defects in hematopoiesis. Comparative molecular analysis of wild-type and Htt-null retinoic acid-differentiated cells revealed gene network dysregulation associated with organ development that nominate polycomb repressive complexes and miRNAs as molecular mediators. Together these findings demonstrate that Htt is required both pre- and post-gastrulation to support normal development.

Type: Article
Title: Hypomorphic mutation of the mouse Huntington's disease gene orthologue
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pgen.1007765
Publisher version: https://doi.org/10.1371/journal.pgen.1007765
Language: English
Additional information: Copyright © 2019 Murthy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Embryos, MicroRNAs, Gene expression, Alleles, Cell differentiation, Ears, Hematopoiesis, Mutation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10074083
Downloads since deposit
76Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item