Generation and Characterization of Knock-in Mouse Models Expressing Versions of Huntingtin with Either an N17 or a Combined PolyQ and Proline-Rich Region Deletion.

ABSTRACT:

Background

The polyglutamine (polyQ) stretch of the Huntingtin protein (HTT) in mammals is flanked by a highly conserved 17 amino acid N-terminal domain (N17), and a proline-rich region (PRR). The PRR is a binding site for many HTT-interacting proteins, and the N17 domain regulates several normal HTT functions, including HTT's ability to associate with membranes and organelles.

Objective

This study investigates the consequence of deleting mouse Huntingtin's (Htt's) N17 domain or a combination of its polyQ stretch and PRR (QP) on normal Htt function in mice.

Methods

Knock-in mice expressing versions of Htt lacking either the N17 domain (HttΔN17) or both the polyQ and PRR domains (HttΔQP) were generated, and their behavior, autophagy function, and neuropathology were ev

SUBMITTER: Andre EA 

PROVIDER: S-EPMC5389044 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature