TY - JOUR
T1 - Tom1l2 hypomorphic mice exhibit increased incidence of infections and tumors and abnormal immunologic response
AU - Girirajan, Santhosh
AU - Hauck, Paula M.
AU - Williams, Stephen
AU - Vlangos, Christopher N.
AU - Szomju, Barbara B.
AU - Solaymani-Kohal, Sara
AU - Mosier, Philip D.
AU - White, Kimber L.
AU - McCoy, Kathleen
AU - Elsea, Sarah H.
N1 - Funding Information:
The authors thank Dr. Mario Dance from the VCU Department of Animal Resources for helping with collection of blood samples from mice. They acknowledge Valerie Vinoverski for assistance with GFP studies and Constance B. Hartmann for technical assistance with immunofluorescence staining and flow cytometry. They also thank the Transgenic Animal Model Core at the University of Michigan, the Histopathology Core at Michigan State University, and the Comparative Pathology Lab at UC Davis for mouse tissue and serum studies. This work was supported in part by NIH R01HD38534 (SHE), NIH P50DA05275 (KM), NIH R01ES07199 (KM), the Jeffress Foundation (SHE), the A. D. Williams Trust Fund (KM & SHE), and by resources from Michigan State University and Virginia Commonwealth University.
PY - 2008/4
Y1 - 2008/4
N2 - 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.
AB - 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.
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U2 - 10.1007/s00335-008-9100-6
DO - 10.1007/s00335-008-9100-6
M3 - Article
C2 - 18343975
AN - SCOPUS:42449119665
SN - 0938-8990
VL - 19
SP - 246
EP - 262
JO - Mammalian Genome
JF - Mammalian Genome
IS - 4
ER -