(A) Schematic of the first Sec24a mutant allele (Sec24agt). Gray blocks represent exons with specific numbers indicated. SA, splice acceptor cassette; β-Geo, β-galactosidase-neo fusion; pA, poly-adenylation sequence. F, R, and V represent genotyping primers. Bottom, sequence of Sec24agt gene trap insertion junction; sequence of the gene trap cassette is underlined. (B) RT-PCR detection of splicing between exons 2 and 3 in Sec24agt/gt mice. Liver cDNA of wild type mice was serially diluted into liver cDNA of Sec24agt/gt mice as indicated and used as template for PCR with primers Sec24a-Exon2 and Sec24a-Exon3 (see primer sequences). (C) Loss of SEC24A protein in Sec24agt/gt mice. Upper panel, PCR genotyping; lower panel, immunoblotting of brain protein extracts from mice with the genotypes indicated at the top, using the indicated SEC24A-D antibodies. (D) Body weights of SEC24A-deficient and wild type control mice. HF, high fat diet. Error bars represent SEM (standard error of the mean). At least six mice were included in each group at each time point. (E) Kaplan Meier plot for survival of SEC24A-deficient mice (n = 20) and littermate controls (n = 15). (F) Histology of several tissues from Sec24agt/gt mice. Li, liver; H, heart; K, kidney; Lu, lung.