Creatine transport and pathological changes in creatine transporter deficient mice
| Autor: | Steven Andrew Baker, Hannes Vogel, Thomas J. Montine, Jeffrey J. Nirschl, Chandresh R. Gajera, Adam M. Wawro |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Endogeny Creatine transport Tandem mass spectrometry Creatine Plasma Membrane Neurotransmitter Transport Proteins 03 medical and health sciences chemistry.chemical_compound Mice Tandem Mass Spectrometry Internal medicine Genetics medicine Deficient mouse Animals Pathological Genetics (clinical) 030304 developmental biology Mice Knockout 0303 health sciences Chemistry 030305 genetics & heredity Skeletal muscle Brain Diseases Metabolic Inborn Transporter Endocrinology medicine.anatomical_structure Mental Retardation X-Linked Chromatography Liquid |
| Zdroj: | Journal of inherited metabolic diseaseREFERENCES. 44(4) |
| ISSN: | 1573-2665 |
| Popis: | The severe impact on brain function and lack of effective therapy for patients with creatine (Cr) transporter deficiency motivated the generation of three ubiquitous Slc6a8 deficient mice (-/y). While each mouse knock-out line has similar behavioral effects at 2 to 3 months of age, other features critical to the efficient use of these mice in drug discovery are unclear or lacking: the concentration of Cr in brain and heart differ widely between mouse lines, there are limited data on histopathologic changes, and no data on Cr uptake. Here, we determined survival, measured endogenous Cr and uptake of its deuterium-labeled analogue Cr-d3 using a liquid chromatography coupled with tandem mass spectrometry assay, and performed comprehensive histopathologic examination on the Slc6a8-/y mouse developed by Skelton et. al. Our results show that Slc6a8-/y mice have widely varying organ-specific uptake of Cr-d3, significantly diminished growth with the exception of brain, progressive vacuolar myopathy, and markedly shortened lifespan. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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