Hypomorphic mutation of the mouse Huntington's disease gene orthologue.
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, (Hdhneo...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-03-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC6445486?pdf=render |
| _version_ | 1818162935280697344 |
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| author | Vidya Murthy Toma Tebaldi Toshimi Yoshida Serkan Erdin Teresa Calzonetti Ravi Vijayvargia Takshashila Tripathi Emanuela Kerschbamer Ihn Sik Seong Alessandro Quattrone Michael E Talkowski James F Gusella Katia Georgopoulos Marcy E MacDonald Marta Biagioli |
| author_facet | Vidya Murthy Toma Tebaldi Toshimi Yoshida Serkan Erdin Teresa Calzonetti Ravi Vijayvargia Takshashila Tripathi Emanuela Kerschbamer Ihn Sik Seong Alessandro Quattrone Michael E Talkowski James F Gusella Katia Georgopoulos Marcy E MacDonald Marta Biagioli |
| author_sort | Vidya Murthy |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T16:41:34Z |
| format | Article |
| id | doaj.art-a8a2369e6b384c22a37f9ec74a3b79d1 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-11T16:41:34Z |
| publishDate | 2019-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-a8a2369e6b384c22a37f9ec74a3b79d12022-12-22T00:58:19ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042019-03-01153e100776510.1371/journal.pgen.1007765Hypomorphic mutation of the mouse Huntington's disease gene orthologue.Vidya MurthyToma TebaldiToshimi YoshidaSerkan ErdinTeresa CalzonettiRavi VijayvargiaTakshashila TripathiEmanuela KerschbamerIhn Sik SeongAlessandro QuattroneMichael E TalkowskiJames F GusellaKatia GeorgopoulosMarcy E MacDonaldMarta BiagioliRare 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.http://europepmc.org/articles/PMC6445486?pdf=render |
| spellingShingle | Vidya Murthy Toma Tebaldi Toshimi Yoshida Serkan Erdin Teresa Calzonetti Ravi Vijayvargia Takshashila Tripathi Emanuela Kerschbamer Ihn Sik Seong Alessandro Quattrone Michael E Talkowski James F Gusella Katia Georgopoulos Marcy E MacDonald Marta Biagioli Hypomorphic mutation of the mouse Huntington's disease gene orthologue. PLoS Genetics |
| title | Hypomorphic mutation of the mouse Huntington's disease gene orthologue. |
| title_full | Hypomorphic mutation of the mouse Huntington's disease gene orthologue. |
| title_fullStr | Hypomorphic mutation of the mouse Huntington's disease gene orthologue. |
| title_full_unstemmed | Hypomorphic mutation of the mouse Huntington's disease gene orthologue. |
| title_short | Hypomorphic mutation of the mouse Huntington's disease gene orthologue. |
| title_sort | hypomorphic mutation of the mouse huntington s disease gene orthologue |
| url | http://europepmc.org/articles/PMC6445486?pdf=render |
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