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Ablation of TRalpha...
Ablation of TRalpha2 and a concomitant overexpression of alpha1 yields a mixed hypo- and hyperthyroid phenotype in mice.
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- Saltó, C (författare)
- Karolinska Institutet
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- Kindblom, Jenny, 1971 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin,Institute of Internal Medicine
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- Johansson, C (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi,Institute of Physiology and Pharmacology, Dept of Physiology
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Wang, Z. (författare)
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Gullberg, H (författare)
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Nordström, Kristina (författare)
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Mansén, A (författare)
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- Ohlsson, Claes, 1965 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för internmedicin,Institute of Internal Medicine, Dept of Medicine
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- Thorén, Peter (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi,Institute of Physiology and Pharmacology, Dept of Physiology
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Forrest, D (författare)
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- Vennström, Björn (författare)
- Karolinska Institutet
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(creator_code:org_t)
- The Endocrine Society, 2001
- 2001
- Engelska.
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Ingår i: Molecular endocrinology (Baltimore, Md.). - : The Endocrine Society. - 0888-8809. ; 15:12, s. 2115-28
- Relaterad länk:
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https://gup.ub.gu.se...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Thyroid hormone governs a diverse repertoire of physiological functions through receptors encoded in the receptor genes alpha and beta, which each generate variant proteins. In mammals, the alpha gene generates, in addition to the normal receptor TRalpha1, a non-hormone-binding variant TRalpha2 whose exact function is unclear. Here, we present the phenotype associated with the targeted ablation of TRalpha2 expression. Selective ablation of TRalpha2 resulted in an inevitable, concomitant overexpression of TRalpha1. Both TRalpha2 +/- and -/- mice show a complex phenotype with low levels of free T3 and free T4, and have inappropriately normal levels of TSH. The thyroid glands exhibit mild morphological signs of dysfunction and respond poorly to TSH, suggesting that the genetic changes affect the ability of the gland to release thyroid hormones. However, the phenotype of the mutant mice also has features of hyperthyroidism, including decreased body weight, elevated heart rate, and a raised body temperature. Furthermore, TRalpha2-/- and TRalpha2+/- mice are obese and exhibit skeletal alterations, associated with a late-onset growth retardation. The results thus suggest that the overexpression of TRalpha1 and the concomitant decrease in TRalpha2 expression lead to a mixed hyper- and hypothyroid phenotype, dependent on the tissue studied. The phenotypes suggest that the balance of TRalpha1:TRalpha2 expressed from the TRalpha gene provides an additional level of tuning the control of growth and homeostasis in mammalian species.
Nyckelord
- Animals
- Blotting
- Northern
- Body Composition
- Bone Density
- Crosses
- Genetic
- DNA-Binding Proteins
- biosynthesis
- genetics
- physiology
- Female
- Gene Expression Regulation
- physiology
- Histocytochemistry
- Hyperthyroidism
- genetics
- metabolism
- Hypothyroidism
- genetics
- metabolism
- Male
- Mice
- Mice
- Inbred BALB C
- Mice
- Knockout
- Phenotype
- RNA
- chemistry
- isolation & purification
- Receptors
- Cytoplasmic and Nuclear
- biosynthesis
- genetics
- physiology
- Receptors
- Thyroid Hormone
- Reverse Transcriptase Polymerase Chain Reaction
- Telemetry
- Thyroxine
- blood
- Triiodothyronine
- blood
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Saltó, C
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Kindblom, Jenny, ...
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Johansson, C
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Wang, Z.
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Gullberg, H
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Nordström, Krist ...
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visa fler...
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Mansén, A
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Ohlsson, Claes, ...
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Thorén, Peter
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Forrest, D
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Vennström, Björn
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visa färre...
- Artiklar i publikationen
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Molecular endocr ...
- Av lärosätet
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Göteborgs universitet
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Karolinska Institutet