Figure 1.

The schematic diagram of the alleles of mouse models used in this study. (A) Structure of the wild type (WT) locus of the Naglu and Hsd17b1 genes showing 6 exons presented as black boxes for both the Naglu and Hsd17b1 genes. (B) The targeted allele in Hsd17b1-LacZ/Neo mice with a deleted Hsd17b1 gene, including the targeting vector containing the lacZ and neo cassette¹³. (C) The targeted allele in Hsd17b1-LacZ mice, produced by crossing the Hsd17b1-LacZ/Neo mice with the Rosa26 transgenic mouse strain¹⁴. (D) Transgenic mice ubiquitously expressing the human HSD17B1 gene¹⁶ were crossed with Hsd17b1-LacZ/Neo mice to bring the HSD17B1 enzyme activity to an unrelated locus. In the HSD17B1 transgenic mice, human HSD17B1 cDNA was inserted between the CMV-enhanced chicken beta-actin promoter and rabbit beta-globin poly-A tail. (E) The targeted allele in Naglu-Neo mice¹⁵, showing a neo cassette inserted into exon 6. Arrows indicate the genotyping primer sites for all mouse models. (F) The interaction of the Hsd17b1 and Naglu gene region was also studied in vitro using expression constructs including a genomic fragment extending from a region 5 kb upstream of the transcription start site of Naglu until the 3′-region of the Hsd17b1 gene, and using a similar construct of which we deleted 1.8 kb long fragment of the Hsd17b1 gene.