Event Title

Validation of tissue expression and exploration of metabolic phenotypes in hepatocyte-specific huntingtin knockout mice

Co-Author(s)

Kinsella, Fiona; Hovander, Will; Solem, Wes; Bragg, Robert; Legg, Sam; Coffey, Sydney; Cantle, Jeffrey; Carroll, Jeffrey B. (Jeffrey Bryan), 1977-

Research Mentor(s)

Carroll, Jeffrey B. (Jeffrey Bryan), 1977-

Description

Huntington’s disease (HD) is traditionally viewed as a neurodegenerative disease, despite the ubiquitous presence of the causal agent, expanded polyglutamine huntingtin protein (HTT), throughout the body. HD patients can display an array of peripheral symptoms, including metabolic disorders such as weight loss and malabsorption. Further, an understanding of the myriad roles for huntingtin in normal cellular function remains incomplete. In order to better understand the role huntingtin in metabolism, we produced mice in which HTT has been knocked out in hepatocytes (LKO mice). Here we show that LKO mice are born at the expected Mendelian ratio, with western blots confirming that huntingtin knockout is limited to the liver. We find that LKO mice appear grossly normal, but exhibit decreased body weight and length compared to age-matched wildtype mice. We also present results of metabolic phenotyping, including glucose tolerance and insulin tolerance testing. This work contributes to an understanding of the role huntingtin plays in metabolism and raises important safety considerations for HTT lowering therapies targeting the periphery.

Document Type

Event

Start Date

15-5-2019 9:00 AM

End Date

15-5-2019 5:00 PM

Location

Carver Gym (Bellingham, Wash.)

Department

Behavioral Neuroscience

Genre/Form

student projects, posters

Subjects – Topical (LCSH)

Huntington's disease--Research

Type

Image

Rights

Copying of this document in whole or in part is allowable only for scholarly purposes. It is understood, however, that any copying or publication of this document for commercial purposes, or for financial gain, shall not be allowed without the author’s written permission.

Language

English

Format

application/pdf

This document is currently not available here.

Share

COinS
 
May 15th, 9:00 AM May 15th, 5:00 PM

Validation of tissue expression and exploration of metabolic phenotypes in hepatocyte-specific huntingtin knockout mice

Carver Gym (Bellingham, Wash.)

Huntington’s disease (HD) is traditionally viewed as a neurodegenerative disease, despite the ubiquitous presence of the causal agent, expanded polyglutamine huntingtin protein (HTT), throughout the body. HD patients can display an array of peripheral symptoms, including metabolic disorders such as weight loss and malabsorption. Further, an understanding of the myriad roles for huntingtin in normal cellular function remains incomplete. In order to better understand the role huntingtin in metabolism, we produced mice in which HTT has been knocked out in hepatocytes (LKO mice). Here we show that LKO mice are born at the expected Mendelian ratio, with western blots confirming that huntingtin knockout is limited to the liver. We find that LKO mice appear grossly normal, but exhibit decreased body weight and length compared to age-matched wildtype mice. We also present results of metabolic phenotyping, including glucose tolerance and insulin tolerance testing. This work contributes to an understanding of the role huntingtin plays in metabolism and raises important safety considerations for HTT lowering therapies targeting the periphery.