Phenotypic segregation of aphakia and Pitx3-null mutants reveals that Pitx3 deficiency increases consolidation of specific movement components.
Deficiency of the meso-diencephalic dopamine (mdDA) neuron specific transcription factor Pitx3 in aphakia (ak) mice results in the loss of the substantia nigra compacta (SNc). Concomitantly, reduced spontaneous locomotor behavior, symptoms reminiscent to those in Parkinson's disease, has been reported. However, the ak mouse line originates from the 1960s and has been compared to C57BL/6J inbred controls. Therefore, to define Pitx3 gene function in baseline and novelty-induced locomotor behavior and mdDA neuronal activity, we analyzed Pitx3-deficiency in a controlled genetic and epigenetic background. The analysis implicated that, in contrast to the controversial and previously reported hypo-activity in ak mice, Pitx3-/- mice showed normal dark phase motor activity levels. Our data also revealed that ak and Pitx3-/- mice both display a similar neuro-anatomical and physiological phenotype, and, interestingly, showed increased spontaneous home cage activity levels during their habitual sleep phase. Further behavioral analysis revealed that both ak and Pitx3-/- mice have reduced transitions but increased consolidation of specific locomotor behaviors, such as rearing and horizontal movement. Thus, Pitx3 is not involved in the expression of nighttime motor activity levels, but is critical for selective mdDA neuronal activity and associated with increased consolidation of movement.
Kas
Martien J H
MJ
Rudolf Magnus Institute of Neuroscience, Department of Pharmacology and Anatomy, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. m.j.h.kas@umcutrecht.nl
van der Linden
Annemarie J A
AJ
Oppelaar
Hugo
H
von Oerthel
Lars
L
Ramakers
Geert M J
GM
Smidt
Marten P
MP
D000704:Analysis of Variance; D000818:Animals; D001035:Aphakia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology; D018398:Homeodomain Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics*; D010641:Phenotype; D013378:Substantia Nigra / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018398:Homeodomain Proteins; D014157:Transcription Factors; C433629:homeobox protein PITX3; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine