Publications by authors named "S Zeitlin"
Article Synopsis
- Huntington's disease is linked to a toxic increase in the HTT gene's function, prompting the development of therapies targeting HTT reduction in the liver.
- Chronic loss of HTT in mouse liver cells leads to significant physiological changes, such as increased bile acids, cholesterol, and altered liver gene expression patterns.
- Interestingly, the absence of HTT in liver cells also shows resistance to acetaminophen toxicity, suggesting HTT plays a critical role in liver zonation and possibly relates to impaired liver function mechanisms.
Huntington's disease arises from a toxic gain of function in the ( ) gene. As a result, many HTT-lowering therapies are being pursued in clinical studies, including those that reduce HTT RNA and protein expression in the liver. To investigate potential impacts, we characterized molecular, cellular, and metabolic impacts of chronic HTT lowering in mouse hepatocytes.
View Article and Find Full Text PDFWe have developed an inducible Huntington's disease (HD) mouse model that allows temporal control of whole-body allele-specific mutant huntingtin (mHtt) expression. We asked whether moderate global lowering of mHtt (~50%) was sufficient for long-term amelioration of HD-related deficits and, if so, whether early mHtt lowering (before measurable deficits) was required. Both early and late mHtt lowering delayed behavioral dysfunction and mHTT protein aggregation, as measured biochemically.
View Article and Find Full Text PDFHuntington disease (HD) is a monogenic neurodegenerative disorder with one causative gene, huntingtin (HTT). Yet, HD pathobiology is multifactorial, suggesting that cellular factors influence disease progression. Here, we define HTT protein-protein interactions (PPIs) perturbed by the mutant protein with expanded polyglutamine in the mouse striatum, a brain region with selective HD vulnerability.
View Article and Find Full Text PDFCharacterization of a Knock-In Mouse Model with a Huntingtin Exon 1 Deletion.
J Huntingtons Dis
January 2022
Background: The Huntingtin (HTT) N-terminal domains encoded by Huntingtin's (HTT) exon 1 consist of an N17 domain, the polyglutamine (polyQ) stretch and a proline-rich region (PRR). These domains are conserved in mammals and have been hypothesized to modulate HTT's functions in the developing and adult CNS, including DNA damage repair and autophagy.
Objective: This study longitudinally characterizes the in vivo consequences of deleting the murine Htt N-terminal domains encoded by Htt exon 1.