title: Coxsackievirus and adenovirus receptor is essential for cardiomyocyte development.
abstract: The coxsackievirus and adenovirus receptor (CAR) is a transmembrane protein that is known to be a site of viral attachment and entry, but its physiologic functions are undefined. CAR expression is maximal in neonates and wanes rapidly after birth in organs such as heart, muscle, and brain, suggesting that CAR plays a role in the development of these tissues. Here, we show that CAR deficiency resulted in an embryonic lethal condition associated with cardiac defects. Specifically, commencing approximately 10.5 days postconception (dpc), CAR-/- cardiomyocytes exhibited regional apoptosis evidenced by both histopathologic features of cell death and positive staining for the apoptotic marker cleaved caspase 3. CAR-/- fetuses invariably suffered from degeneration of the myocardial wall and thoracic hemorrhaging, leading to death by 11.5 dpc. These findings are consistent with the view that CAR provides positive survival signals to cardiomyocytes that are essential for normal heart development.
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Damon R
authors.initials: DR
authors.lastname: Asher
authors.forename: Anna M
authors.initials: AM
authors.lastname: Cerny
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Weiler
authors.forename: James W
authors.initials: JW
authors.lastname: Horner
authors.forename: Marilyn L
authors.initials: ML
authors.lastname: Keeler
authors.forename: Mychell A
authors.initials: MA
authors.lastname: Neptune
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Jones
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Depinho
authors.forename: Robert W
authors.initials: RW
authors.lastname: Finberg
mesh_terms: D000818:Animals; D001483:Base Sequence; D002678:Chimera; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D005333:Fetus / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006321:Heart / Q000196:embryology* / Q000254:growth & development; D006330:Heart Defects, Congenital / Q000209:etiology / Q000473:pathology; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000502:physiology*
chemical_list: C568772:CLMP protein, mouse; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D012333:RNA, Messenger; D011991:Receptors, Virus