PMID- 28211815
OWN - NLM
STAT- MEDLINE
DCOM- 20171023
LR  - 20181205
IS  - 1879-6400 (Electronic)
IS  - 1879-6397 (Print)
IS  - 1879-6397 (Linking)
VI  - 6
IP  - 1
DP  - 2017
TI  - 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.
PG  - 47-62
LID - 10.3233/JHD-160231 [doi]
AB  - 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 (HttDeltaN17) or both the polyQ and PRR domains (HttDeltaQP) were 
      generated, and their behavior, autophagy function, and neuropathology were 
      evaluated. RESULTS: Homozygous and hemizygous HttDeltaQP/DeltaQP, HttDeltaN17/DeltaN17, HttDeltaQP/-, 
      and HttDeltaN17/- mice were generated at the expected Mendelian frequency. HttDeltaQP/DeltaQP 
      mutants exhibit improvements in motor coordination compared to controls (Htt+/+). 
      In contrast, HttDeltaN17/DeltaN17 mutants do not exhibit any changes in motor 
      coordination, but they do display variable changes in spatial learning that are 
      dependent on their age at testing. Neither mutant exhibited any changes in basal 
      autophagy in comparison to controls, but thalamostriatal synapses in the dorsal 
      striatum of 24-month-old HttDeltaN17/DeltaN17 mice were decreased compared to controls. 
      CONCLUSIONS: These findings support the hypothesis that Htt's N17 and QP domains 
      are dispensable for its critical functions during early embryonic development, 
      but are likely more important for Htt functions in CNS development or 
      maintenance.
FAU - Andre, Emily A
AU  - Andre EA
FAU - Braatz, Elise M
AU  - Braatz EM
FAU - Liu, Jeh-Ping
AU  - Liu JP
FAU - Zeitlin, Scott O
AU  - Zeitlin SO
LA  - eng
GR  - F31 NS083289/NS/NINDS NIH HHS/United States
GR  - R01 NS043466/NS/NINDS NIH HHS/United States
GR  - R01 NS077926/NS/NINDS NIH HHS/United States
GR  - R56 NS043466/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - Netherlands
TA  - J Huntingtons Dis
JT  - Journal of Huntington's disease
JID - 101589965
RN  - 0 (Htt protein, mouse)
RN  - 0 (Huntingtin Protein)
RN  - 0 (Peptides)
RN  - 26700-71-0 (polyglutamine)
RN  - 9DLQ4CIU6V (Proline)
SB  - IM
MH  - Animals
MH  - Autophagy/physiology
MH  - Brain/growth & development/*metabolism/pathology
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Gene Knock-In Techniques
MH  - Huntingtin Protein/*genetics/metabolism
MH  - Huntington Disease/*genetics/*metabolism/pathology
MH  - Male
MH  - Maze Learning/physiology
MH  - Mice, 129 Strain
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Neurons/*metabolism/pathology
MH  - Peptides/genetics
MH  - Proline/genetics
MH  - Protein Domains
MH  - *Sequence Deletion
PMC - PMC5389044
OTO - NOTNLM
OT  - Huntingtin
OT  - Huntington's disease
OT  - N17
OT  - PSD 95
OT  - Vglut2
OT  - autophagy
OT  - polyQ
OT  - proline-rich region
EDAT- 2017/02/18 06:00
MHDA- 2017/10/24 06:00
CRDT- 2017/02/18 06:00
PHST- 2017/02/18 06:00 [pubmed]
PHST- 2017/10/24 06:00 [medline]
PHST- 2017/02/18 06:00 [entrez]
AID - JHD160231 [pii]
AID - 10.3233/JHD-160231 [doi]
PST - ppublish
SO  - J Huntingtons Dis. 2017;6(1):47-62. doi: 10.3233/JHD-160231.