title: Expression of Coxsackie-Adenovirus receptor (CAR) in the developing mouse olfactory system.
abstract: Interest in manipulating gene expression in olfactory sensory neurons (OSNs) has led to the use of adenoviruses (AdV) as gene delivery vectors. OSNs are the first order neurons in the olfactory system and the initial site of odor detection. They are highly susceptible to adenovirus infection although the mechanism is poorly understood. The Coxsackie-Adenovirus receptor (CAR) and members of the integrin family have been implicated in the process of AdV infection in various systems. Multiple serotypes of AdV efficiently bind to the CAR, leading to entry and infection of the host cell by a mechanism that can also involve integrins. Cell lines that do not express CAR are relatively resistant, but not completely immune to AdV infection, suggesting that other mechanisms participate in mediating AdV attachment and entry. Using in situ hybridization and western blot analyses, we show that OSNs and olfactory bulbs (OB) of mice express abundant CAR mRNA at embryonic and neonatal stages, with progressive diminution during postnatal development. By contrast to the olfactory epithelium (OE), CAR mRNA is still present in the adult mouse OB. Furthermore, despite a similar postnatal decline, CAR protein expression in the OE and OB of mice continues into adulthood. Our results suggest that the robust AdV infection observed in the postnatal olfactory system is mediated by CAR and that expression of even small amounts of CAR protein as seen in the adult rodent, permits efficient AdV infection and entry. CAR is an immunoglobulin domain-containing protein that bears homology to cell-adhesion molecules suggesting the possibility that it may participate in organization of the developing olfactory system.
authors.affiliation: Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, 21201, USA.
authors.forename: Giri
authors.initials: G
authors.lastname: Venkatraman
authors.forename: Maik
authors.initials: M
authors.lastname: Behrens
authors.forename: Martina
authors.initials: M
authors.lastname: Pyrski
authors.forename: Frank L
authors.initials: FL
authors.lastname: Margolis
mesh_terms: D000257:Adenoviridae Infections / Q000503:physiopathology; D000367:Age Factors; D000818:Animals; D001483:Base Sequence; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009830:Olfactory Bulb / Q000196:embryology / Q000254:growth & development* / Q000502:physiology*; D009831:Olfactory Mucosa / Q000196:embryology / Q000254:growth & development* / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D011991:Receptors, Virus / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C568772:CLMP protein, mouse; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D012333:RNA, Messenger; D011991:Receptors, Virus