Open AccessTransgenic mice expressing a human mutant β1 thyroid receptor are hyperactive, impulsive, and inattentive
Author(s) -
Siesser W. B.,
Zhao J.,
Miller L. R.,
Cheng S.Y.,
McDonald M. P.
Publication year - 2006
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/j.1601-183x.2005.00161.x
Subject(s) - genetically modified mouse , methylphenidate , impulsivity , transgene , attention deficit hyperactivity disorder , psychology , euthyroid , endocrinology , thyroid , phenotype , medicine , neuroscience , psychiatry , biology , genetics , gene
Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed childhood psychiatric disorder. We have found that a transgenic mouse bearing a human mutant thyroid receptor (TRβ1) expresses all of the defining symptoms of ADHD—inattention, hyperactivity, and impulsivity—as well as a ‘paradoxical’ response to methylphenidate (MPH). As with ADHD, the behavioral phenotypes expressed by the TRβ transgenic mice are dynamic and sensitive to changes in environmental conditions, stress, and reinforcement. TRβ transgenic mice are euthyroid except for a brief period during postnatal development, but the behavioral phenotypes, elevated dopamine turnover, and paradoxical response to MPH persist into adulthood. Thus, like the vast majority of children with ADHD, the TRβ transgenic mice exhibit the symptoms of ADHD in the complete absence of thyroid abnormalities. This suggests that even transient perturbations in developmental thyroid homeostasis can have long‐lasting behavioral and cognitive consequences, including producing the full spectrum of symptoms of ADHD.