T-cell dependent response (TDAR)
To assess the role of the PPAR in the humoral response to a T-cell-dependent antigen, B6.129S4-Ppartm1GonzN12 (PPAR KO) and background-matched wild-type (WT) C57BL/6-Tac female mice were purchased from Taconic Farms (Rensselaer, NY). The vendor website (http://www.taconic.com/cs/Satellite?

blobcol¼urldocument&blobkey¼id&blobtable=TA_Document &blobwhere¼1347208841885&ssbinary¼true) includes a detailed description of the KO strain.
All animals were delivered to animal facilities at the USEPA that are accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC). All animals were 6–7-weeks-of-age at delivery. Once at the USEPA, the animals were housed in poly-carbonate cages with hardwood chip bedding (Beta Chip) in groups of six (PPAR KO andWT) or four (C57BL/6N) and allowed to acclimate for at least 10 days before dosing began. They were provided a 12-h light:dark cycle (light, 06:00–18:00 hours; dark, 18:00–06:00 hours), maintained at 22.3 [± 1.1]C and 40–60% relative humidity, and given ad libitum access to both food (5P00 Prolab RMH 3000, PMI Nutrition International, Richmond, IN) and water. The Institutional Animal Care and Use Committee of the National Health and Environmental Effects Research Laboratory, US EPA, approved all procedures in advance.

WT and PPAR KO mice were immunized on the 11th day of dosing (0, 7.5, or 30 mg PFOA/kg/day) by intravenous injection of 4.0107 SRBC in 0.2 ml of sterile saline. Five days later (the peak of IgM response to SRBC in C57BL/6 mice) and 1 day after dosing ended, the mice were euthanized by CO2 inhalation and exsanguinated by neck vein transection. Blood was collected, held at room temperature for 30 min, and then centrifuged at 4 C to separate serum. The sera were then frozen at 80 C until analysis of IgM antibody titers.

Female C57BL/6-Tac (wild-type) mice

HAWC