Mutation of fgr causes hepatomegaly and steatosis. (A) The viral insertion (white box) in the intron between exons 11 and 12 of the fgr gene in hi1532B mutants results in a gene trap cassette of 172 bp (gt, dark green) following bp 1286 of the fgr-coding sequence (grey box). The resulting transcript encodes a message that is frame shifted so that a stop codon is created following the gene trap sequence. (B) cDNA prepared from wild-type appearing embryos and their mutant siblings from a hi1532B was amplified with primers that span the trap (arrows on the mRNA diagram in A). As two-thirds of the wild-type appearing embryos from a hi1532B clutch are heterozygous for the mutant allele, both transcripts from the trapped allele (green arrow) in addition to transcripts the wild-type allele (black arrow) are amplified in these embryos. The mutant embryos only contain transcripts encoding the trap. Histology from wild-type (C) and mutant (D) day 5 embryos illustrates the large hepatocytes that are filled with vesicles. Several acidophilic bodies (asterisks) representing dead cells as well as those with condensed DNA and nuclear fragmentation (arrow) are evident in mutant livers, but are never observed in wild-type embryos. (E,F) ORO staining of wild-type (E) and mutant (F) livers from day 5 embryos reveals substantial steatosis in fgr mutant hepatocytes. Scale bar: 50 µm.
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