title: Tom1l2 hypomorphic mice exhibit increased incidence of infections and tumors and abnormal immunologic response.
abstract: Studies have shown that the TOM1 family of proteins, including TOM1 and TOM1L1, are actively involved in endosomal trafficking and function in the immune response. However, much less is known about the function of TOM1L2. To understand the biological importance of TOM1L2 and the potential significance of its cellular role, we created and evaluated Tom1l2 gene-trapped mice with reduced Tom1l2 expression. Mice hypomorphic for Tom1l2 exhibited numerous infections and tumors compared to wild-type littermates. Associated with this increased risk for infection and tumor formation, apparently healthy Tom1l2 hypomorphs also had splenomegaly, elevated B- and T-cell counts, and an impaired humoral response, although at a reduced penetrance. Furthermore, cellular localization studies showed that a Tom1l2-GFP fusion protein colocalizes with Golgi compartments, supporting the role of Tom1l2 in cellular trafficking, while molecular modeling and bioinformatic analysis of Tom1l2 illustrated a structural basis for a functional role in trafficking. These results indicate a role for Tom1l2 in the immune response and possibly in tumor suppression.
authors.affiliation: Department of Human Genetics, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Santhosh
authors.initials: S
authors.lastname: Girirajan
authors.forename: Paula M
authors.initials: PM
authors.lastname: Hauck
authors.forename: Stephen
authors.initials: S
authors.lastname: Williams
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Vlangos
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Szomju
authors.forename: Sara
authors.initials: S
authors.lastname: Solaymani-Kohal
authors.forename: Philip D
authors.initials: PD
authors.lastname: Mosier
authors.forename: Kimber L
authors.initials: KL
authors.lastname: White
authors.forename: Kathleen
authors.initials: K
authors.lastname: McCoy
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Elsea
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal; D019556:COS Cells; D002522:Chlorocebus aethiops; D018390:Gene Targeting; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D021381:Protein Transport; D016415:Sequence Alignment; D012756:Sheep; D013154:Spleen / Q000276:immunology / Q000473:pathology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1