title: Nab2 maintains thymus cellularity with aging and stress.
abstract: Thymic cellularity is influenced by a variety of biological and environmental factors, such as age and stress; however, little is known about the molecular genetic mechanisms that regulate this process. Immediate early genes of the Early growth response (Egr) family have critical roles in immune function and response to environmental stress. The transcription factors, Egr1, Egr2 and Egr3, play roles in the thymus and in peripheral T-cell activation. Nab2, which binds Egrs 1, 2, and 3 as a co-regulator of transcription, also regulates peripheral T-cell activation. However, a role for Nab2 in the thymus has not been reported. Using Nab2-deficient (KO) mice we found that male Nab2KO mice have reduced thymus size and decreased numbers of thymocytes, compared with age-matched wildtype (WT) mice. Furthermore, the number of thymocytes in Nab2KO males decreases more rapidly with age. This effect is sex-dependent as female Nab2KO mice show neither reduced thymocyte numbers nor accelerated thymocyte loss with age, compared to female WT littermates. Since stress induces expression of Nab2 and the Egrs, we examined whether loss of Nab2 alters stress-induced decrease in thymic cellularity. Restraint stress induced a significant decrease in thymic cellularity in Nab2KO and WT mice, with significant changes in the thymocyte subset populations only in the Nab2KO mice. Stress reduced the percentage of DP cells by half and increased the percentage of CD4SP and CD8SP cells by roughly three-fold in Nab2KO mice. These findings indicate a requirement for Nab2 in maintaining thymocyte number in male mice with age and in response to stress.
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine - Phoenix, 425 N. 5th St., Phoenix, AZ, 85004, USA. Electronic address: khasting@email.arizona.edu.
authors.forename: K Taraszka
authors.initials: KT
authors.lastname: Hastings
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine - Phoenix, 425 N. 5th St., Phoenix, AZ, 85004, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Elizalde
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine - Phoenix, 425 N. 5th St., Phoenix, AZ, 85004, USA.
authors.forename: Leela
authors.initials: L
authors.lastname: Muppana
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine - Phoenix, 425 N. 5th St., Phoenix, AZ, 85004, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Levine
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine - Phoenix, 425 N. 5th St., Phoenix, AZ, 85004, USA.
authors.forename: Christy M
authors.initials: CM
authors.lastname: Kamel
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine - Phoenix, 425 N. 5th St., Phoenix, AZ, 85004, USA.
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Ingram
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine - Phoenix, 425 N. 5th St., Phoenix, AZ, 85004, USA.
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Kirkpatrick
authors.affiliation: Department of Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, 714 E. Van Buren St., Phoenix, AZ, 85004, USA. Electronic address: hucc@email.arizona.edu.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine - Phoenix, 425 N. 5th St., Phoenix, AZ, 85004, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Rausch
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine - Phoenix, 425 N. 5th St., Phoenix, AZ, 85004, USA. Electronic address: amelia@email.arizona.edu.
authors.forename: Amelia L
authors.initials: AL
authors.lastname: Gallitano
mesh_terms: D000375:Aging / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D005260:Female; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism*; D012097:Repressor Proteins / Q000276:immunology / Q000378:metabolism*; D012149:Restraint, Physical; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
chemical_list: C099945:Nab2 protein, mouse; D009363:Neoplasm Proteins; D012097:Repressor Proteins
keywords: Aging; Early growth response gene; Immediate early gene; NGFI-A binding protein; Stress; Thymus