A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Deleting the mouse Hsd17b1 gene results in a hypomorphic Naglu allele and a phenotype mimicking a lysosomal storage disease
Tekijät: Jokela H, Hakkarainen J, Kätkänaho L, Pakarinen P, Ruohonen ST, Tena-Sempere M, Zhang FP, Poutanen M
Kustantaja: NATURE PUBLISHING GROUP
Julkaisuvuosi: 2017
Journal: Scientific Reports
Tietokannassa oleva lehden nimi: SCIENTIFIC REPORTS
Lehden akronyymi: SCI REP-UK
Artikkelin numero: ARTN 16406
Vuosikerta: 7
Aloitussivu: 1
Lopetussivu: 12
Sivujen määrä: 12
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-017-16618-5
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/28603129
HSD17B1 is a steroid metabolising enzyme. We have previously generated knockout mice that had the entire coding region of Hsd17b1 replaced with lacZ-neo cassette (Hsd17b1-LacZ/Neo mice). This resulted in a 90% reduction of HSD17B1 activity, associated with severe subfertility in the knockout females. The present study indicates that Hsd17b1-LacZ/Neo male mice have a metabolic phenotype, including reduced adipose mass, increased lean mass and lipid accumulation in the liver. During the characterisation of this metabolic phenotype, it became evident that the expression of the Naglu gene, located closely upstream of Hsd17b1, was severely reduced in all tissues analysed. Similar results were obtained from Hsd17b1-LacZ mice after removing the neo cassette from the locus or by crossing the Hsd17b1-LacZ/Neo mice with transgenic mice constitutively expressing human HSD17B1. The deficiency of Naglu caused the accumulation of glycosaminoglycans in all studied mouse models lacking the Hsd17b1 gene. The metabolic phenotypes of the Hsd17b1 knockout mouse models were recapitulated in Naglu knockout mice. Based on the data we propose that the Hsd17b1 gene includes a regulatory element controlling Naglu expression and the metabolic phenotype in mice lacking the Hsd17b1 genomic region is caused by the reduced expression of Naglu rather than the lack of Hsd17b1.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
