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Transgenic mice exp...
Transgenic mice expressing fibroblast growth factor 23 under the control of the alpha1(I) collagen promoter exhibit growth retardation, osteomalacia, and disturbed phosphate homeostasis.
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- Larsson, Tobias, 1974 (author)
- Uppsala universitet,Gothenburg University,Göteborgs universitet,Institutionen för kemi,Department of Chemistry,Institutionen för medicinska vetenskaper
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- Marsell, Richard (author)
- Uppsala universitet,Ortopedi
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Schipani, Ernestina (author)
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- Ohlsson, Claes, 1965 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för internmedicin,Institute of Internal Medicine, Dept of Medicine
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- Ljunggren, Östen (author)
- Uppsala universitet,Endokrinologi och mineralmetabolism
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Tenenhouse, Harriet S (author)
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Jüppner, Harald (author)
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- Jonsson, Kenneth B (author)
- Uppsala universitet,Ortopedi
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(creator_code:org_t)
- The Endocrine Society, 2004
- 2004
- English.
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In: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 145:7, s. 3087-94
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Abstract
Subject headings
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- Mutations in the fibroblast growth factor 23 gene, FGF23, cause autosomal dominant hypophosphatemic rickets (ADHR). The gene product, FGF-23, is produced by tumors from patients with oncogenic osteomalacia (OOM), circulates at increased levels in most patients with X-linked hypophosphatemia (XLH) and is phosphaturic when injected into rats or mice, suggesting involvement in the regulation of phosphate (Pi) homeostasis. To better define the precise role of FGF-23 in maintaining Pi balance and bone mineralization, we generated transgenic mice that express wild-type human FGF-23, under the control of the alpha1(I) collagen promoter, in cells of the osteoblastic lineage. At 8 wk of age, transgenic mice were smaller (body weight = 17.5 +/- 0.57 vs. 24.3 +/- 0.37 g), exhibited decreased serum Pi concentrations (1.91 +/- 0.27 vs. 2.75 +/- 0.22 mmol/liter) and increased urinary Pi excretion when compared with wild-type littermates. The serum concentrations of human FGF-23 (undetectable in wild-type mice) was markedly elevated in transgenic mice (>7800 reference units/ml). Serum PTH levels were increased in transgenic mice (231 +/- 62 vs. 139 +/- 44 pg/ml), whereas differences in calcium and 1,25-dihydroxyvitamin D were not apparent. Expression of Npt2a, the major renal Na(+)/Pi cotransporter, as well as Npt1 and Npt2c mRNAs, was significantly decreased in the kidneys of transgenic mice. Histology of tibiae displayed a disorganized and widened growth plate and peripheral quantitative computerized tomography analysis revealed reduced bone mineral density in transgenic mice. The data indicate that FGF-23 induces phenotypic changes in mice resembling those of patients with ADHR, OOM, and XLH and that FGF-23 is an important determinant of Pi homeostasis and bone mineralization.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
Keyword
- Animals
- Bone and Bones
- pathology
- physiology
- Calcification
- Physiologic
- Calcium
- blood
- urine
- Collagen Type I
- genetics
- Fibroblast Growth Factors
- genetics
- metabolism
- Growth Disorders
- metabolism
- pathology
- physiopathology
- Homeostasis
- physiology
- Humans
- Kidney
- cytology
- physiology
- Mice
- Mice
- Inbred C57BL
- Mice
- Inbred CBA
- Mice
- Transgenic
- Osteomalacia
- metabolism
- pathology
- physiopathology
- Parathyroid Glands
- pathology
- physiology
- Phenotype
- Phosphates
- blood
- urine
- Promoter Regions (Genetics)
- Vitamin D
- metabolism
- Orthopaedics
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Larsson, Tobias, ...
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Marsell, Richard
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Schipani, Ernest ...
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Ohlsson, Claes, ...
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Ljunggren, Östen
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Tenenhouse, Harr ...
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show more...
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Jüppner, Harald
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Jonsson, Kenneth ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Surgery
- Articles in the publication
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Endocrinology
- By the university
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University of Gothenburg
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Uppsala University