TY  - JOUR
AU  - Neuner, Sarah M
AU  - Garfinkel, Benjamin P
AU  - Wilmott, Lynda A
AU  - Ignatowska-Jankowska, Bogna M
AU  - Citri, Ami
AU  - Orly, Joseph
AU  - Lu, Lu
AU  - Overall, Rupert W
AU  - Kempermann, Gerd
AU  - Mulligan, Megan K
AU  - Williams, Robert W
AU  - O'Connell, Kristen M S
AU  - Kaczorowski, Catherine C
TI  - Systems genetics identifies Hp1bp3 as a novel modulator of cognitive aging.
JO  - Neurobiology of aging
VL  - 46
SN  - 0197-4580
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - DZNE-2020-05183
SP  - 58-67
PY  - 2016
AB  - An individual's genetic makeup plays an important role in determining susceptibility to cognitive aging. Identifying the specific genes that contribute to cognitive aging may aid in early diagnosis of at-risk patients, as well as identify novel therapeutics targets to treat or prevent development of symptoms. Challenges to identifying these specific genes in human studies include complex genetics, difficulty in controlling environmental factors, and limited access to human brain tissue. Here, we identify Hp1bp3 as a novel modulator of cognitive aging using a genetically diverse population of mice and confirm that HP1BP3 protein levels are significantly reduced in the hippocampi of cognitively impaired elderly humans relative to cognitively intact controls. Deletion of functional Hp1bp3 in mice recapitulates memory deficits characteristic of aged impaired mice and humans, further supporting the idea that Hp1bp3 and associated molecular networks are modulators of cognitive aging. Overall, our results suggest Hp1bp3 may serve as a potential target against cognitive aging and demonstrate the utility of genetically diverse animal models for the study of complex human disease.
KW  - Aging: genetics
KW  - Animals
KW  - Cognition: physiology
KW  - Cognition Disorders: genetics
KW  - Cognition Disorders: psychology
KW  - Cognitive Aging: physiology
KW  - Conditioning, Psychological: physiology
KW  - Disease Models, Animal
KW  - Fear
KW  - Female
KW  - Genetic Association Studies
KW  - Genetic Predisposition to Disease: genetics
KW  - Humans
KW  - Male
KW  - Memory: physiology
KW  - Memory Disorders: genetics
KW  - Memory Disorders: psychology
KW  - Mice
KW  - Mice, Knockout
KW  - Nuclear Proteins: physiology
KW  - HP1BP3 protein, mouse (NLM Chemicals)
KW  - Nuclear Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:27460150
C2  - pmc:PMC5018442
DO  - DOI:10.1016/j.neurobiolaging.2016.06.008
UR  - https://pub.dzne.de/record/138861
ER  -