Behavioral deficits and progressive neuropathology in progranulin-deficient mice

A mouse model of frontotemporal dementia

Fangfang Yin, Magali Dumont, Rebecca Banerjee, Yao Ma, Huihong Li, Michael T. Lin, M. Flint Beal, Carl Nathan, Bobby Thomas, Aihao Ding

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Progranulin haploinsufficiency causes frontotemporal dementia with tau-negative, ubiquitin-positive neuronal inclusion pathology. In this study, we showed that progranulin-deficient mice displayed increased depression- and disinhibition-like behavior, as well as deficits in social recognition from a relatively young age. These mice did not have any deficit in locomotion or exploration. Eighteen-month-old progranulin-deficient mice demonstrated impaired spatial learning and memory in the Morris water maze. In addition to behavioral deficits, progranulin-deficient mice showed a progressive development of neuropathology from 12 mo of age, including enhanced activation of microglia and astrocytes and ubiquitination and cytoplasmic accumulation of phosphorylated TDP-43. Thus, progranulin deficiency induced FTD-like behavioral and neuropathological deficits. These mice may serve as an important tool for deciphering underlying mechanisms in frontotemporal dementia.

Original languageEnglish (US)
Pages (from-to)4639-4647
Number of pages9
JournalFASEB Journal
Volume24
Issue number12
DOIs
StatePublished - Dec 1 2010

Fingerprint

Frontotemporal Dementia
Pathology
Ubiquitin
Chemical activation
Data storage equipment
Water
Haploinsufficiency
Ubiquitination
Microglia
Locomotion
Astrocytes
Neuropathology
Depression

Keywords

  • Neurodegeneration
  • TDP-43
  • Transgenic mice
  • Ubiquitin

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Behavioral deficits and progressive neuropathology in progranulin-deficient mice : A mouse model of frontotemporal dementia. / Yin, Fangfang; Dumont, Magali; Banerjee, Rebecca; Ma, Yao; Li, Huihong; Lin, Michael T.; Beal, M. Flint; Nathan, Carl; Thomas, Bobby; Ding, Aihao.

In: FASEB Journal, Vol. 24, No. 12, 01.12.2010, p. 4639-4647.

Research output: Contribution to journalArticle

Yin, F, Dumont, M, Banerjee, R, Ma, Y, Li, H, Lin, MT, Beal, MF, Nathan, C, Thomas, B & Ding, A 2010, 'Behavioral deficits and progressive neuropathology in progranulin-deficient mice: A mouse model of frontotemporal dementia', FASEB Journal, vol. 24, no. 12, pp. 4639-4647. https://doi.org/10.1096/fj.10-161471
Yin, Fangfang ; Dumont, Magali ; Banerjee, Rebecca ; Ma, Yao ; Li, Huihong ; Lin, Michael T. ; Beal, M. Flint ; Nathan, Carl ; Thomas, Bobby ; Ding, Aihao. / Behavioral deficits and progressive neuropathology in progranulin-deficient mice : A mouse model of frontotemporal dementia. In: FASEB Journal. 2010 ; Vol. 24, No. 12. pp. 4639-4647.
@article{9037354857984ded81fa98365fd706cd,
title = "Behavioral deficits and progressive neuropathology in progranulin-deficient mice: A mouse model of frontotemporal dementia",
abstract = "Progranulin haploinsufficiency causes frontotemporal dementia with tau-negative, ubiquitin-positive neuronal inclusion pathology. In this study, we showed that progranulin-deficient mice displayed increased depression- and disinhibition-like behavior, as well as deficits in social recognition from a relatively young age. These mice did not have any deficit in locomotion or exploration. Eighteen-month-old progranulin-deficient mice demonstrated impaired spatial learning and memory in the Morris water maze. In addition to behavioral deficits, progranulin-deficient mice showed a progressive development of neuropathology from 12 mo of age, including enhanced activation of microglia and astrocytes and ubiquitination and cytoplasmic accumulation of phosphorylated TDP-43. Thus, progranulin deficiency induced FTD-like behavioral and neuropathological deficits. These mice may serve as an important tool for deciphering underlying mechanisms in frontotemporal dementia.",
keywords = "Neurodegeneration, TDP-43, Transgenic mice, Ubiquitin",
author = "Fangfang Yin and Magali Dumont and Rebecca Banerjee and Yao Ma and Huihong Li and Lin, {Michael T.} and Beal, {M. Flint} and Carl Nathan and Bobby Thomas and Aihao Ding",
year = "2010",
month = "12",
day = "1",
doi = "10.1096/fj.10-161471",
language = "English (US)",
volume = "24",
pages = "4639--4647",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "12",

}

TY - JOUR

T1 - Behavioral deficits and progressive neuropathology in progranulin-deficient mice

T2 - A mouse model of frontotemporal dementia

AU - Yin, Fangfang

AU - Dumont, Magali

AU - Banerjee, Rebecca

AU - Ma, Yao

AU - Li, Huihong

AU - Lin, Michael T.

AU - Beal, M. Flint

AU - Nathan, Carl

AU - Thomas, Bobby

AU - Ding, Aihao

PY - 2010/12/1

Y1 - 2010/12/1

N2 - Progranulin haploinsufficiency causes frontotemporal dementia with tau-negative, ubiquitin-positive neuronal inclusion pathology. In this study, we showed that progranulin-deficient mice displayed increased depression- and disinhibition-like behavior, as well as deficits in social recognition from a relatively young age. These mice did not have any deficit in locomotion or exploration. Eighteen-month-old progranulin-deficient mice demonstrated impaired spatial learning and memory in the Morris water maze. In addition to behavioral deficits, progranulin-deficient mice showed a progressive development of neuropathology from 12 mo of age, including enhanced activation of microglia and astrocytes and ubiquitination and cytoplasmic accumulation of phosphorylated TDP-43. Thus, progranulin deficiency induced FTD-like behavioral and neuropathological deficits. These mice may serve as an important tool for deciphering underlying mechanisms in frontotemporal dementia.

AB - Progranulin haploinsufficiency causes frontotemporal dementia with tau-negative, ubiquitin-positive neuronal inclusion pathology. In this study, we showed that progranulin-deficient mice displayed increased depression- and disinhibition-like behavior, as well as deficits in social recognition from a relatively young age. These mice did not have any deficit in locomotion or exploration. Eighteen-month-old progranulin-deficient mice demonstrated impaired spatial learning and memory in the Morris water maze. In addition to behavioral deficits, progranulin-deficient mice showed a progressive development of neuropathology from 12 mo of age, including enhanced activation of microglia and astrocytes and ubiquitination and cytoplasmic accumulation of phosphorylated TDP-43. Thus, progranulin deficiency induced FTD-like behavioral and neuropathological deficits. These mice may serve as an important tool for deciphering underlying mechanisms in frontotemporal dementia.

KW - Neurodegeneration

KW - TDP-43

KW - Transgenic mice

KW - Ubiquitin

UR - http://www.scopus.com/inward/record.url?scp=78149296002&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78149296002&partnerID=8YFLogxK

U2 - 10.1096/fj.10-161471

DO - 10.1096/fj.10-161471

M3 - Article

VL - 24

SP - 4639

EP - 4647

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 12

ER -