FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2897858902> ?p ?o ?g. }

• W2897858902 abstract "Abstract Rare individuals with hypomorphic inactivating mutations in the Huntington’s Disease (HD) gene ( HTT ), identified by CAG repeat expansion in the eponymous neurodegenerative disorder, exhibit variable abnormalities that imply HTT essential roles during organ development. Here we report phenotypes produced when increasingly severe hypomorphic mutations in Htt , the murine HTT orthologue (in Hdh neoQ20 , Hdh neoQ50 , Hdh neoQ111 mice), were placed over a null allele ( Hdh ex4/5 ). The most severe hypomorphic allele failed to rescue null lethality at gastrulation, while the intermediate alleles yielded 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 and proposed polycomb repressive complexes and miRNAs as molecular mediators. Together these findings demonstrate that the HD gene acts both pre- and post-gastrulation and possibly suggest pleiotropic consequences of HTT -lowering therapeutic strategies. Author Summary The HTT gene product mutated in Huntington’s Disease (HD) has essential roles during normal organism development, however, still not fully predictable are the functional consequences of its partial inactivation. Our genetic study provides a comprehensive effects’ description of progressively stronger suppression of Htt gene, the murine HTT counterpart. The most severe Htt reduction leads to embryo lethality, while intermediate Htt dosages yield a variety of developmental abnormalities affecting body size, skin, skeletal and ear formation, and hematopoiesis. Complementing molecular analysis in differentiating cells depleted of a functional Htt gene further elucidates genes’ networks dysregulated during organ development and proposes chromatin regulators and short non-coding RNAs as key molecular mediators. Together these findings demonstrate that the HD gene acts both at early and later stages of development, thus possibly suggesting long-term consequences associated to the newest HD therapeutic strategies aimed at lowering the HTT gene product." @default.
• W2897858902 created "2018-10-26" @default.
• W2897858902 creator A5002300255 @default.
• W2897858902 creator A5004831350 @default.
• W2897858902 creator A5026731634 @default.
• W2897858902 creator A5035104823 @default.
• W2897858902 creator A5042816307 @default.
• W2897858902 creator A5044329623 @default.
• W2897858902 creator A5055791363 @default.
• W2897858902 creator A5058757082 @default.
• W2897858902 creator A5060291693 @default.
• W2897858902 creator A5074068870 @default.
• W2897858902 creator A5074179127 @default.
• W2897858902 creator A5080707778 @default.
• W2897858902 creator A5083076717 @default.
• W2897858902 creator A5085732836 @default.
• W2897858902 creator A5090004774 @default.
• W2897858902 date "2018-10-15" @default.
• W2897858902 modified "2023-10-16" @default.
• W2897858902 title "Hypomorphic mutation of the mouse Huntington’s disease gene orthologue" @default.
• W2897858902 cites W102000198 @default.
• W2897858902 cites W1846721807 @default.
• W2897858902 cites W1895398290 @default.
• W2897858902 cites W1905627141 @default.
• W2897858902 cites W1968839521 @default.
• W2897858902 cites W1977983193 @default.
• W2897858902 cites W1978337436 @default.
• W2897858902 cites W1978940920 @default.
• W2897858902 cites W1995008214 @default.
• W2897858902 cites W1998336645 @default.
• W2897858902 cites W2001736065 @default.
• W2897858902 cites W2002644780 @default.
• W2897858902 cites W2002923824 @default.
• W2897858902 cites W2021549489 @default.
• W2897858902 cites W2028967783 @default.
• W2897858902 cites W2029073164 @default.
• W2897858902 cites W2030410903 @default.
• W2897858902 cites W2035144346 @default.
• W2897858902 cites W2035618305 @default.
• W2897858902 cites W2040213004 @default.
• W2897858902 cites W2044559546 @default.
• W2897858902 cites W2048254671 @default.
• W2897858902 cites W2057619579 @default.
• W2897858902 cites W2071146976 @default.
• W2897858902 cites W2077327925 @default.
• W2897858902 cites W2080174669 @default.
• W2897858902 cites W2080777953 @default.
• W2897858902 cites W2082501455 @default.
• W2897858902 cites W2084120869 @default.
• W2897858902 cites W2092234690 @default.
• W2897858902 cites W2092707982 @default.
• W2897858902 cites W2095860692 @default.
• W2897858902 cites W2108003276 @default.
• W2897858902 cites W2108234281 @default.
• W2897858902 cites W2113390076 @default.
• W2897858902 cites W2113534197 @default.
• W2897858902 cites W2114104545 @default.
• W2897858902 cites W2121642311 @default.
• W2897858902 cites W2123275897 @default.
• W2897858902 cites W2123791127 @default.
• W2897858902 cites W2124940469 @default.
• W2897858902 cites W2125661978 @default.
• W2897858902 cites W2133395347 @default.
• W2897858902 cites W2136427957 @default.
• W2897858902 cites W2148611562 @default.
• W2897858902 cites W2152045787 @default.
• W2897858902 cites W2153159217 @default.
• W2897858902 cites W2158945342 @default.
• W2897858902 cites W2160777380 @default.
• W2897858902 cites W2163112976 @default.
• W2897858902 cites W2165944043 @default.
• W2897858902 cites W2167250543 @default.
• W2897858902 cites W2174734928 @default.
• W2897858902 cites W2229294739 @default.
• W2897858902 cites W2267328205 @default.
• W2897858902 cites W2295033318 @default.
• W2897858902 cites W2464267557 @default.
• W2897858902 cites W2514189710 @default.
• W2897858902 cites W2610342468 @default.
• W2897858902 cites W2734837988 @default.
• W2897858902 cites W2750346204 @default.
• W2897858902 cites W2793425651 @default.
• W2897858902 cites W4247053599 @default.
• W2897858902 cites W4300038072 @default.
• W2897858902 cites W84114990 @default.
• W2897858902 doi "https://doi.org/10.1101/444059" @default.
• W2897858902 hasPublicationYear "2018" @default.
• W2897858902 type Work @default.
• W2897858902 sameAs 2897858902 @default.
• W2897858902 citedByCount "0" @default.
• W2897858902 crossrefType "posted-content" @default.
• W2897858902 hasAuthorship W2897858902A5002300255 @default.
• W2897858902 hasAuthorship W2897858902A5004831350 @default.
• W2897858902 hasAuthorship W2897858902A5026731634 @default.
• W2897858902 hasAuthorship W2897858902A5035104823 @default.
• W2897858902 hasAuthorship W2897858902A5042816307 @default.
• W2897858902 hasAuthorship W2897858902A5044329623 @default.
• W2897858902 hasAuthorship W2897858902A5055791363 @default.
• W2897858902 hasAuthorship W2897858902A5058757082 @default.
• W2897858902 hasAuthorship W2897858902A5060291693 @default.

• next