Behavioral and regulatory abnormalities in mice deficient in the NPAS1 and NPAS3 transcription factors.
Laboratory mice bearing inactivating mutations in the genes encoding the NPAS1 and NPAS3 transcription factors have been shown to exhibit a spectrum of behavioral and neurochemical abnormalities. Behavioral abnormalities included diminished startle response, as measured by prepulse inhibition, and impaired social recognition. NPAS1/NPAS3-deficient mice also exhibited stereotypic darting behavior at weaning and increased locomotor activity. Immunohistochemical staining assays showed that the NPAS1 and NPAS3 proteins are expressed in inhibitory interneurons and that the viability and anatomical distribution of these neurons are unaffected by the absence of either transcription factor. Adult brain tissues from NPAS3- and NPAS1/NPAS3-deficient mice exhibited a distinct reduction in reelin, a large, secreted protein whose expression has been reported to be attenuated in the postmortem brain tissue of patients with schizophrenia. These observations raise the possibility that a regulatory program controlled in inhibitory interneurons by the NPAS1 and NPAS3 transcription factors may be either substantively or tangentially relevant to psychosis.
Erbel-Sieler
Claudia
C
Departments of Biochemistry and Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Dudley
Carol
C
Zhou
Yudong
Y
Wu
Xinle
X
Estill
Sandi Jo
SJ
Han
Tina
T
Diaz-Arrastia
Ramon
R
Brunskill
Eric W
EW
Potter
S Steven
SS
McKnight
Steven L
SL
D000375:Aging / Q000502:physiology; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D012919:Social Behavior; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D014157:Transcription Factors; D005680:gamma-Aminobutyric Acid; C512770:Npas1 protein, mouse; C492587:Npas3 protein, mouse; C000717128:Reln protein, mouse