Pituitary Tumor Transforming Gene 1 Orchestrates Gene Regulatory Variation in Mouse Ventral Midbrain During Aging

Document Type

Article

Publication Date

1-1-2020

Institution/Department

Maine Medical Center Research Institute

Journal Title

Front Genet

MeSH Headings

Mice, Animals, Pituitary Neoplasms, Mesencephalon, Genes, Regulator, Aging

Abstract

Dopaminergic neurons in the midbrain are of particular interest due to their role in diseases such as Parkinson's disease and schizophrenia. Genetic variation between individuals can affect the integrity and function of dopaminergic neurons but the DNA variants and molecular cascades modulating dopaminergic neurons and other cells types of ventral midbrain remain poorly defined. Three genetically diverse inbred mouse strains - C57BL/6J, A/J, and DBA/2J - differ significantly in their genomes (∼7 million variants), motor and cognitive behavior, and susceptibility to neurotoxins. To further dissect the underlying molecular networks responsible for these variable phenotypes, we generated RNA-seq and ChIP-seq data from ventral midbrains of the 3 mouse strains. We defined 1000-1200 transcripts that are differentially expressed among them. These widespread differences may be due to altered activity or expression of upstream transcription factors. Interestingly, transcription factors were significantly underrepresented among the differentially expressed genes, and only one transcription factor,

ISSN

1664-8021

First Page

566734

Last Page

566734

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