title: Overexpression of Batf induces an apoptotic defect and an associated lymphoproliferative disorder in mice.
abstract: Activator protein-1 (AP-1) is a dimeric transcription factor composed of the Jun, Fos and Atf families of proteins. Batf is expressed in the immune system and participates in AP-1 dimers that modulate gene expression in response to a variety of stimuli. Transgenic (Tg) mice overexpressing human BATF in T cells were generated using the human CD2 promoter (CD2-HA (hemagglutinin antigen) - BATF). By 1 year of age, over 90% of the mice developed a lymphoproliferative disorder (LPD). The enlarged lymph nodes characteristic of this LPD contain a polyclonal accumulation of T cells with a CD4(+) bias, yet efforts to propagate these tumor cells in vitro demonstrate that they do not proliferate as well as wild-type CD4(+) T cells. Instead, the accumulation of these cells is likely due to an apoptotic defect as CD2-HA-BATF Tg T cells challenged by trophic factor withdrawal in vitro resist apoptosis and display a pro-survival pattern of Bcl-2 family protein expression. As elevated levels of Batf expression are a feature of lymphoid tumors in both humans and mice, these observations support the use of CD2-HA-BATF mice as a model for investigating the molecular details of apoptotic dysregulation in LPD.
authors.affiliation: Department of Biological Sciences, College of Science, Purdue University, West Lafayette, IN 47907-2064, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Logan
authors.forename: K L
authors.initials: KL
authors.lastname: Jordan-Williams
authors.forename: S
authors.initials: S
authors.lastname: Poston
authors.forename: J
authors.initials: J
authors.lastname: Liao
authors.forename: E J
authors.initials: EJ
authors.lastname: Taparowsky
mesh_terms: D000818:Animals; D017209:Apoptosis; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018801:CD2 Antigens / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D006388:Hemagglutinins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: C099359:BATF protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D018801:CD2 Antigens; D006388:Hemagglutinins; D019253:Proto-Oncogene Proteins c-bcl-2; D018808:Transcription Factor AP-1; D053148:Caspase 3