Matches in SemOpenAlex for { <https://semopenalex.org/work/W4210369939> ?p ?o ?g. }
- W4210369939 endingPage "1192.e7" @default.
- W4210369939 startingPage "1173" @default.
- W4210369939 abstract "In Huntington's disease (HD), the uninterrupted CAG repeat length, but not the polyglutamine length, predicts disease onset. However, the underlying pathobiology remains unclear. Here, we developed bacterial artificial chromosome (BAC) transgenic mice expressing human mutant huntingtin (mHTT) with uninterrupted, and somatically unstable, CAG repeats that exhibit progressive disease-related phenotypes. Unlike prior mHTT transgenic models with stable, CAA-interrupted, polyglutamine-encoding repeats, BAC-CAG mice show robust striatum-selective nuclear inclusions and transcriptional dysregulation resembling those in murine huntingtin knockin models and HD patients. Importantly, the striatal transcriptionopathy in HD models is significantly correlated with their uninterrupted CAG repeat length but not polyglutamine length. Finally, among the pathogenic entities originating from mHTT genomic transgenes and only present or enriched in the uninterrupted CAG repeat model, somatic CAG repeat instability and nuclear mHTT aggregation are best correlated with early-onset striatum-selective molecular pathogenesis and locomotor and sleep deficits, while repeat RNA-associated pathologies and repeat-associated non-AUG (RAN) translation may play less selective or late pathogenic roles, respectively." @default.
- W4210369939 created "2022-02-08" @default.
- W4210369939 creator A5000192581 @default.
- W4210369939 creator A5002483385 @default.
- W4210369939 creator A5003079920 @default.
- W4210369939 creator A5007737622 @default.
- W4210369939 creator A5008135470 @default.
- W4210369939 creator A5010465278 @default.
- W4210369939 creator A5020296130 @default.
- W4210369939 creator A5023215972 @default.
- W4210369939 creator A5027548043 @default.
- W4210369939 creator A5034054400 @default.
- W4210369939 creator A5035018795 @default.
- W4210369939 creator A5039252463 @default.
- W4210369939 creator A5049454660 @default.
- W4210369939 creator A5052012618 @default.
- W4210369939 creator A5062316104 @default.
- W4210369939 creator A5075336895 @default.
- W4210369939 creator A5078220100 @default.
- W4210369939 creator A5078308965 @default.
- W4210369939 creator A5079779162 @default.
- W4210369939 creator A5080439207 @default.
- W4210369939 creator A5086920221 @default.
- W4210369939 date "2022-04-01" @default.
- W4210369939 modified "2023-10-18" @default.
- W4210369939 title "Uninterrupted CAG repeat drives striatum-selective transcriptionopathy and nuclear pathogenesis in human Huntingtin BAC mice" @default.
- W4210369939 cites W1037002207 @default.
- W4210369939 cites W1569891543 @default.
- W4210369939 cites W1606672690 @default.
- W4210369939 cites W1895398290 @default.
- W4210369939 cites W1970986383 @default.
- W4210369939 cites W1973830626 @default.
- W4210369939 cites W1982024899 @default.
- W4210369939 cites W1985474993 @default.
- W4210369939 cites W1993938423 @default.
- W4210369939 cites W1995051993 @default.
- W4210369939 cites W1997188614 @default.
- W4210369939 cites W2004901342 @default.
- W4210369939 cites W2019592351 @default.
- W4210369939 cites W2020117714 @default.
- W4210369939 cites W2023627547 @default.
- W4210369939 cites W2024097058 @default.
- W4210369939 cites W2026722283 @default.
- W4210369939 cites W2029399677 @default.
- W4210369939 cites W2040271470 @default.
- W4210369939 cites W2050558334 @default.
- W4210369939 cites W2051577979 @default.
- W4210369939 cites W2051897382 @default.
- W4210369939 cites W2074836283 @default.
- W4210369939 cites W2075147732 @default.
- W4210369939 cites W2077225885 @default.
- W4210369939 cites W2081245925 @default.
- W4210369939 cites W2082458878 @default.
- W4210369939 cites W2083076780 @default.
- W4210369939 cites W2087990951 @default.
- W4210369939 cites W2091011066 @default.
- W4210369939 cites W2091718095 @default.
- W4210369939 cites W2105303722 @default.
- W4210369939 cites W2107514471 @default.
- W4210369939 cites W2108345226 @default.
- W4210369939 cites W2108570063 @default.
- W4210369939 cites W2109249715 @default.
- W4210369939 cites W2111468080 @default.
- W4210369939 cites W2113964087 @default.
- W4210369939 cites W2118546680 @default.
- W4210369939 cites W2121642311 @default.
- W4210369939 cites W2126357344 @default.
- W4210369939 cites W2126877059 @default.
- W4210369939 cites W2127313039 @default.
- W4210369939 cites W2128517811 @default.
- W4210369939 cites W2130668838 @default.
- W4210369939 cites W2133890709 @default.
- W4210369939 cites W2153992384 @default.
- W4210369939 cites W2158174988 @default.
- W4210369939 cites W2160748841 @default.
- W4210369939 cites W2168133967 @default.
- W4210369939 cites W2169101662 @default.
- W4210369939 cites W2169456326 @default.
- W4210369939 cites W2170256902 @default.
- W4210369939 cites W2171165237 @default.
- W4210369939 cites W2179438025 @default.
- W4210369939 cites W2181090621 @default.
- W4210369939 cites W2206699319 @default.
- W4210369939 cites W2273942450 @default.
- W4210369939 cites W2274495055 @default.
- W4210369939 cites W2346092180 @default.
- W4210369939 cites W2567931568 @default.
- W4210369939 cites W2609055977 @default.
- W4210369939 cites W2617594926 @default.
- W4210369939 cites W2680511221 @default.
- W4210369939 cites W2749718288 @default.
- W4210369939 cites W2767573351 @default.
- W4210369939 cites W2786866790 @default.
- W4210369939 cites W2790905337 @default.
- W4210369939 cites W2790983771 @default.
- W4210369939 cites W2794248168 @default.
- W4210369939 cites W2804663373 @default.
- W4210369939 cites W2887748872 @default.