title: Mice depleted of the coxsackievirus and adenovirus receptor display normal spermatogenesis and an intact blood-testis barrier.
abstract: The coxsackievirus and adenovirus receptor (CXADR (CAR)) is a cell adhesion molecule expressed mainly in epithelial cells. Numerous evidence indicate that CXADR has an important role in testis development and function of the blood-testis barrier (BTB) in vitro. The role of CXADR in testis physiology in vivo has, however, not been addressed. We therefore constructed a conditional CXADR knockout (cKO) mouse model in which CXADR can be depleted at any chosen timepoint by the administration of tamoxifen. We report for the first time that testicular depletion of CXADR in adult and pubertal mice does not alter BTB permeability or germ cell migration across the BTB during spermatogenesis. Adult cKO mice display normal junctional ultra-structure and localization of the junctional proteins claudin-3, occludin, junction-associated molecule-A (JAM-A), and ZO1. The BTB was intact with no leakage of biotin and lanthanum tracers into the tubular lumen. Adult CXADR cKO mice were fertile with normal sperm parameters and litter size. Breeding experiments and genotyping of the pups demonstrated that CXADR-negative sperm could fertilize WT eggs. In addition, knocking down CXADR from postnatal day 9 (P9) does not affect testicular development and BTB formation. These cKO mice were analyzed at P49 and P90 and display an intact barrier and uncompromised fertility. We conclude that CXADR possesses no direct role in testicular physiology in vivo.
authors.affiliation: Paediatric Endocrinology UnitDepartment of Women's and Children's HealthDepartment of Biosciences and NutritionNovumDepartment of Physiology and PharmacologyKarolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Taranum
authors.initials: T
authors.lastname: Sultana
authors.affiliation: Paediatric Endocrinology UnitDepartment of Women's and Children's HealthDepartment of Biosciences and NutritionNovumDepartment of Physiology and PharmacologyKarolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Mi
authors.initials: M
authors.lastname: Hou
authors.affiliation: Paediatric Endocrinology UnitDepartment of Women's and Children's HealthDepartment of Biosciences and NutritionNovumDepartment of Physiology and PharmacologyKarolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Jan-Bernd
authors.initials: JB
authors.lastname: Stukenborg
authors.affiliation: Paediatric Endocrinology UnitDepartment of Women's and Children's HealthDepartment of Biosciences and NutritionNovumDepartment of Physiology and PharmacologyKarolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Virpi
authors.initials: V
authors.lastname: Töhönen
authors.affiliation: Paediatric Endocrinology UnitDepartment of Women's and Children's HealthDepartment of Biosciences and NutritionNovumDepartment of Physiology and PharmacologyKarolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Jose
authors.initials: J
authors.lastname: Inzunza
authors.affiliation: Paediatric Endocrinology UnitDepartment of Women's and Children's HealthDepartment of Biosciences and NutritionNovumDepartment of Physiology and PharmacologyKarolinska Institutet, Karolinska University Hospital, 17176 Stockholm, SwedenPaediatric Endocrinology UnitDepartment of Women's and Children's HealthDepartment of Biosciences and NutritionNovumDepartment of Physiology and PharmacologyKarolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Andrei S
authors.initials: AS
authors.lastname: Chagin
authors.affiliation: Paediatric Endocrinology UnitDepartment of Women's and Children's HealthDepartment of Biosciences and NutritionNovumDepartment of Physiology and PharmacologyKarolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden kerstin.sollerbrant@ki.se.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Sollerbrant
mesh_terms: D000367:Age Factors; D000818:Animals; D001814:Blood-Testis Barrier / Q000378:metabolism* / Q000648:ultrastructure; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000172:deficiency* / Q000235:genetics; D005260:Female; D005298:Fertility; D007365:Intercellular Junctions / Q000378:metabolism; D008098:Litter Size; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010539:Permeability; D011247:Pregnancy; D012741:Sexual Maturation; D013091:Spermatogenesis; D013094:Spermatozoa / Q000378:metabolism*; D062725:Tight Junction Proteins / Q000378:metabolism
chemical_list: C568772:CLMP protein, mouse; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D062725:Tight Junction Proteins