| 1. |
- Jokela, Heli, et al.
(författare)
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Deleting the mouse Hsd17b1 gene results in a hypomorphic Naglu allele and a phenotype mimicking a lysosomal storage disease.
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Pallon, Jan, et al.
(författare)
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Feasibility Study of Gel Filtration as a Separation Method for Blood Serum Proteins in Combination with PIXE Analysis
- 1987
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Ingår i: Biological Trace Element Research. - 1559-0720. ; 12:1, s. 401-409
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Tidskriftsartikel (refereegranskat)abstract
- The combination between a protein separation technique and the PIXE method has a great potential for large surveys, including thousands of samples, in which multielemental analysis is required. Gel filtration with a Sephadex G-200 gel and a TRIS-acetate buffer was used for separating proteins in human serum. The fractions were doped with an yttrium/vanadium standard and then concentrated and pipeted onto Kimfol™ backing foils. Using the PIXE technique, the distributions of Fe, Cu, Zn, and Se, with respect to molecular size, were found, indicating binding to specific proteins. Sulfur and phosphorus were found to correlate well with the protein content measured by UV-absorption at 280 nm. Further developments and tests on the protein separation technique is required, taking restrictions imposed by the PIXE method into consideration.
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| 3. |
- Pallon, Jan, et al.
(författare)
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Metodik för snabba multielementanalyser av biologiskt material
- 1984
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Avsikten med detta projekt har varit att utveckla väl fungerande rutiner för PIXE-analys av biologiska prov med anknytning till exponering i arbetsmiljösituationer. Kravet på metoderna är att de tillvaratar PIXE-metodens fördelar (multielementanalys, små prov, snabb analys, låga detektionsgränser) och samtidigt förändrar eller förstör så lite som möjligt av den information som finns i de ursprungliga biologiska proven under de behandlingssteg som är nödvändiga före analysen. Ett antal standardrutiner har utvecklats med vilka man kan hantera prov som blod, lever, njure och liknande. Direkt analys av enskilda hårstrån och nagelprov kan göras utan förbehandling. Avsikten är att dessa vävnader till viss del skall tjäna som personliga monitorer för exponering,. För detta ändamål, liksom för studier av elementprofiler i hud har även protonmikrostråleteknik utnyttjats. Försök med selektiv koncentrering av vissa ämnen i urin liksom separation av serumproteiner har gjorts. Avsikten med det sistnämnda är att finna om metallbindande protein kan användas som exponeringsindikator. I det följande redogörs kortfattat för principerna, de olika prepareringsmetoderna och vilka provtyper de tillämpats på. De hänvisningar till figurer som görs syftar till figurer i slutet av rapporten.
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| 4. |
- Pallon, Jan, et al.
(författare)
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PIXE Analysis of Blood Serum Proteins, Separated by Gel Filtration
- 1984
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Ingår i: Nuclear Instruments and Methods in Physics Research B. ; 3:1-3, s. 373-376
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Tidskriftsartikel (refereegranskat)abstract
- Gel filtration of blood serum was carried out with Sephadex G-200 gel and tris buffer at pH 7.8. The amount of protein in each of about 100 collected fractions was monitored using UV absorption. The fractions were concentrated and deposited onto Kimfol backing foils. From the PIXE results distributions of S, Fe, Cu and Zn were obtained in relation to the protein peaks, while elements like K, Ca and Br appeared at the position corresponding to small molecular sizes. Quantification, taking into account the intermediate thicknesses of the samples, gave reasonable values. By adjusting the pH of the tris buffer with acetate instead of HCl, an increase in sensitivity was achieved, as the Cl is an important source of electron bremsstrahlung. By low temperature ashing still better detection limits can be reached, but at the expense of the loss of volatile elements.
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| 5. |
- Strauss, Leena, et al.
(författare)
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Seminal vesicles and urinary bladder as sites of aromatization of androgens in men, evidenced by a CYP19A1-driven luciferase reporter mouse and human tissue specimens.
- 2013
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 27:4, s. 1342-50
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Tidskriftsartikel (refereegranskat)abstract
- The human CYP19A1 gene is expressed in various tissues by the use of tissue-specific promoters, whereas the rodent cyp19a1 gene is expressed mainly in the gonads and brain. We generated a transgenic mouse model containing a >100-kb 5' region of human CYP19A1 gene connected to a luciferase reporter gene. The luciferase activity in mouse tissues mimicked the CYP19A1 gene expression pattern in humans. Interestingly, the reporter gene activity was 16 and 160 times higher in the urinary bladder and seminal vesicles, respectively, as compared with the activity in the testis. Accordingly, CYP19A1 gene and P450arom protein expression was detected in those human tissues. Moreover, the data revealed that the expression of CYP19A1 gene is driven by promoters PII, I.4, and I.3 in the seminal vesicles, and by promoters PII and I.4 in the urinary bladder. Furthermore, the reporter gene expression in the seminal vesicles was androgen dependent: Castration decreased the expression ∼20 times, and testosterone treatment restored it to the level of an intact mouse. This reporter mouse model facilitates studies of tissue-specific regulation of the human CYP19A1 gene, and our data provide evidence for seminal vesicles as important sites for estrogen production in males.-Strauss, L., Rantakari, P., Sjögren, K., Salminen, A., Lauren, E., Kallio, J., Damdimopoulou, P., Boström, M., Boström, P. J., Pakarinen, P., Zhang, F. P., Kujala, P., Ohlsson, C., Mäkelä, S., Poutanen, M. Seminal vesicles and urinary bladder as sites of aromatization of androgens in men, evidenced by a CYP19A1-driven luciferase reporter mouse and human tissue specimens.
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