title: Preservation of cochlear function in Cd39 deficient mice.
abstract: Signalling actions of extracellular nucleotides via P2 receptors influence cellular function in most tissues. In the inner ear, P2 receptor signaling is involved in many processes including the regulation of hearing sensitivity and the cochlea's response to noise stress. CD39 (NTPDase1/ENTPD1) is an ectonucleotidase (ecto-nucleoside triphosphate diphosphohydrolase) that can hydrolyse purine and pyrimidine nucleoside tri- and di-phosphates to generate monophosphate nucleosides. Mice null for Cd39 exhibit major alterations in haemostasis and profound alterations in inflammatory and thrombotic reactions. Studies in the cochlea have suggested the involvement of purinergic-type signals that could be modulated by CD39 in regulation of cochlear blood flow and also auditory neurotransmission. This study aimed to determine the auditory phenotype of adult Cd39 null mice on the C57BL6 background. Auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE) were unaffected in Cd39-deficient mice across the range of test frequencies, suggesting normal neural and outer hair cell function. Mutant mice also showed little difference to wild type mice in vulnerability to acoustic trauma. Gene expression analysis of other membrane-bound NTPDases with comparable hydrolytic activity demonstrated an up-regulation of Entpd2 and Entpd8 in the cochleae of Cd39 deficient mice. These findings suggest that Cd39 deletion alone does not adversely affect cochlear function, possibly as compensatory up-regulation of other surface located NTPDases may offset predicted alterations in cochlear homeostasis.
authors.affiliation: Department of Physiology, The University of Auckland, 85 Park Road, Grafton, Private Bag 92019, Auckland 1142, New Zealand. s.vlajkovic@auckland.ac.nz
authors.forename: Srdjan M
authors.initials: SM
authors.lastname: Vlajkovic
authors.forename: Gary D
authors.initials: GD
authors.lastname: Housley
authors.forename: Peter R
authors.initials: PR
authors.lastname: Thorne
authors.forename: Rita
authors.initials: R
authors.lastname: Gupta
authors.forename: Keiichi
authors.initials: K
authors.lastname: Enjyoji
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cowan
authors.forename: M
authors.initials: M
authors.lastname: Charles Liberman
authors.forename: Simon C
authors.initials: SC
authors.lastname: Robson