title: Regulation of motor function and behavior by atypical chemokine receptor 1.
abstract: Atypical Chemokine Receptor 1 (ACKR1), previously known as Duffy Antigen Receptor for Chemokines, stands out among chemokine receptors for high selective expression on cerebellar Purkinje neurons. Although ACKR1 ligands activate Purkinje cells in vitro, evidence for ACKR1 regulation of brain function in vivo is lacking. Here we demonstrate that Ackr1 (-/-) mice have markedly impaired balance and ataxia on a rotating rod and increased tremor when injected with harmaline, which induces whole-body tremor by activating Purkinje cells. Ackr1 (-/-) mice also exhibited impaired exploratory behavior, increased anxiety-like behavior and frequent episodes of marked hypoactivity under low-stress conditions. Surprisingly, Ackr1 (+/-) had similar behavioral abnormalities, indicating pronounced haploinsufficiency. The behavioral phenotype of Ackr1 (-/-) mice was the opposite of mouse models of cerebellar degeneration, and the defects persisted when Ackr1 was deficient only on non-hematopoietic cells. Together, the results suggest that normal motor function and behavior may partly depend on negative regulation of Purkinje cell activity by Ackr1.
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID)/NIH, Bethesda, MD, USA.
authors.forename: Erich H
authors.initials: EH
authors.lastname: Schneider
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Fowler
authors.forename: Michail S
authors.initials: MS
authors.lastname: Lionakis
authors.forename: Muthulekha
authors.initials: M
authors.lastname: Swamydas
authors.forename: Gibran
authors.initials: G
authors.lastname: Holmes
authors.forename: Vivian
authors.initials: V
authors.lastname: Diaz
authors.forename: Jeeva
authors.initials: J
authors.lastname: Munasinghe
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Peiper
authors.forename: Ji-Liang
authors.initials: JL
authors.lastname: Gao
authors.forename: Philip M
authors.initials: PM
authors.lastname: Murphy
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D004375:Duffy Blood-Group System / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D011689:Purkinje Cells / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D004375:Duffy Blood-Group System; D011956:Receptors, Cell Surface; C483025:Ackr1 protein mouse