Characterisation of Hsd17b14 knockout mice
(English)Manuscript (preprint) (Other academic)
17β hydroxysteroid dehydrogenase (17βHSD) enzymes catalyse the stereospecific oxidation/reduction at carbon 17β of androgens and oestrogens and thereby regulate the pool of bioactive sex hormones. 17βHSD type 14 (17βHSD14) catalyses the inactivation of 17β-hydroxysteroids into their less bioactive 17-keto formation in vitro, however, as the catalytic efficiency of this reaction is relatively low, the question is whether this reaction is the biological role of the enzyme in vivo, or if the enzyme additionally or altogether acts within alternative metabolic pathways. To investigate the role of 17βHSD14 in vivo, we studied the phenotype of a mouse model in which the Hsd17b14 gene had been targeted through homologous recombination. Tissues from male and female mice sacrificed at 3-4 months of age were collected and analysed with regards to gene expression of Hsd17b14 and Hsd17b2 and histological appearance of selected organs. Wild type animals expressed Hsd17b14 in a large number of tissues, peaking in reproductive tissues. Mice globally lacking Hsd17b14 were grossly morphologically identical to their WT counterparts. The histological examination however, revealed impaired mammary gland branching and increased hepatocellular vacuolisation in Hsd1714 knockout animals compared with their WT counterparts. In conclusion, while phenotypical aberrances were absent in most tissues, which may be the result of genetic redundancy or possibly an indication that the gene in question is only modulatory, the main differences, primarily a mammary gland phenotype in female KO mice, implicate disturbed hormonal homeostasis, and thus a role for Hsd17b14 in steroidogenesis in vivo.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-84683OAI: oai:DiVA.org:liu-84683DiVA: diva2:561157