GFAP expression as an indicator of disease severity in mouse models of Alexander disease.

[alexander disease]

AxD (Alexander disease ) is a rare disorder caused by heterozygous mutations in GFAP (glial fibrillary acidic protein ) resulting in accumulation of the GFAP protein and elevation of Gfap mRNA . To test whether GFAP itself can serve as a biomarker of disease status or progression , we investigated two independent measures of GFAP expression in AxD mouse models , one using a genetic reporter of promoter activity and the other quantifying GFAP protein directly in a manner that could also be employed in human studies . Using a transgenic reporter line that expresses firefly luciferase under the control of the murine Gfap promoter (Gfap-luc ), we found that luciferase activity reflected the regional CNS (central nervous system ) variability of Gfap mRNA in Gfap (+/+) mice , and increased in mice containing a point mutation in Gfap that mimics a common human mutation in AxD (R 239 H in the human sequence , and R 236 H in the murine sequence ). In a second set of studies , we quantified GFAP protein in CSF (cerebrospinal fluid ) taken from three different AxD mouse models and littermate controls . GFAP levels in CSF were increased in all three AxD models , in a manner corresponding to the concentrations of GFAP in brain . These studies demonstrate that transactivation of the Gfap promoter is an early and sustained indicator of the disease process in the mouse . Furthermore , GFAP in CSF serves as a potential biomarker that is comparable between mouse models and human patients .

Diseases
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Diseases presenting "sustained indicator of the disease process in the mouse" symptom

alexander disease

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