Deleting the mouse Hsd17b1 gene results in a hypomorphic Naglu allele and a phenotype mimicking a lysosomal storage disease
Copyright policy )Deleting the mouse Hsd17b1 gene results in a hypomorphic Naglu allele and a phenotype mimicking a lysosomal storage disease
AbstractHSD17B1 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.
- University of Córdoba Spain
- University of Turku Finland
- University of Turku Finland
- University of Gothenburg Sweden
- TURUN YLIOPISTO Finland
Male, Genetic association studies, 17-Hydroxysteroid Dehydrogenases, 17-hydroxysteroid dehydrogenases, Gene Expression, Disease models, animal, ta3111, Article, Mice, Mucopolysaccharidosis III, Lysosomal storage diseases, Animals, Glicosaminoglicanos, Alleles, Genetic Association Studies, Enfermedades por almacenamiento Lisosomal, Glycosaminoglycans, Gene deletion, Estudios de asociación genética, Lysosomal Storage Diseases, Disease Models, Animal, Phenotype, Genetic Loci, Sitios genéticos, Gene expression, Lysosomes, Fenotipo, Lisosomas, Gene Deletion, Expresión génica
Male, Genetic association studies, 17-Hydroxysteroid Dehydrogenases, 17-hydroxysteroid dehydrogenases, Gene Expression, Disease models, animal, ta3111, Article, Mice, Mucopolysaccharidosis III, Lysosomal storage diseases, Animals, Glicosaminoglicanos, Alleles, Genetic Association Studies, Enfermedades por almacenamiento Lisosomal, Glycosaminoglycans, Gene deletion, Estudios de asociación genética, Lysosomal Storage Diseases, Disease Models, Animal, Phenotype, Genetic Loci, Sitios genéticos, Gene expression, Lysosomes, Fenotipo, Lisosomas, Gene Deletion, Expresión génica
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).12 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!