title: Comprehensive and differential long-term characterization of the alpha-galactosidase A deficient mouse model of Fabry disease focusing on the sensory system and pain development.
abstract: BACKGROUND
  Fabry disease is an X-linked lysosomal storage disorder due to impaired activity of alpha-galactosidase A with intracellular accumulation of globotriaosylceramide. Associated small fiber pathology leads to characteristic pain in Fabry disease. We systematically assessed sensory system, physical activity, metabolic parameters, and morphology of male and female mice with alpha-galactosidase A deficiency (Fabry ko) from 2 to 27 months of age and compared results with those of age- and gender-matched wild-type littermates of C57Bl/6J background.
  
  
  RESULTS
  From the age of two months, male and female Fabry mice showed mechanical hypersensitivity (p < 0.001 each) compared to wild-type littermates. Young Fabry ko mice of both genders were hypersensitive to heat stimulation (p < 0.01) and developed heat hyposensitivity with aging (p < 0.05), while cold hyposensitivity was present constantly in young (p < 0.01) and old (p < 0.05) Fabry ko mice compared to wild-type littermates. Stride angle increased only in male Fabry ko mice with aging (p < 0.01) in comparison to wild-type littermates. Except for young female mice, male (p < 0.05) and female (p < 0.01) Fabry ko mice had a higher body weight than wild-type littermates. Old male Fabry ko mice were physically less active than their wild-type littermates (p < 0.05), had lower chow intake (p < 0.001), and lost more weight (p < 0.001) in a one-week treadmill experiment than wild-type littermates. Also, Fabry ko mice showed spontaneous pain protective behavior and developed orofacial dysmorphism resembling patients with Fabry disease.
  
  
  CONCLUSIONS
  Mice with alpha-galactosidase A deficiency show age-dependent and distinct deficits of the sensory system. alpha-galactosidase A-deficient mice seem to model human Fabry disease and may be helpful when studying the pathophysiology of Fabry-associated pain.
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany ueceyler_n@ukw.de.
authors.forename: Nurcan
authors.initials: N
authors.lastname: Üçeyler
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.
authors.forename: Lydia
authors.initials: L
authors.lastname: Biko
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Hose
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Hofmann
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommer
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D000795:Fabry Disease / Q000201:enzymology* / Q000503:physiopathology*; D005247:Feeding Behavior; D005260:Female; D005684:Gait; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010146:Pain / Q000503:physiopathology*; D010805:Physical Conditioning, Animal; D012677:Sensation; D013696:Temperature; D014110:Touch; D015431:Weight Loss; D000519:alpha-Galactosidase / Q000378:metabolism*
chemical_list: D000519:alpha-Galactosidase
keywords: Fabry disease; alpha-galactosidase A; mouse model; pain