title: Sex differences of urinary and kidney globotriaosylceramide and lyso-globotriaosylceramide in Fabry mice.
abstract: The aim of our study was to measure globotriaosylceramide (Gb(3)) and lyso-Gb(3) levels by tandem mass spectrometry in the urine and kidney in Fabry (gla knockout) mice and wild-type controls. We found that urine Gb(3) of male and female Fabry mice was higher than wild-type mice of the same sex but also significantly higher in male mice compared with females of the same genotype. In kidney tissue, sex and genotype-dependent differences in Gb(3) levels paralleled those in the urine. Isoforms C16, C22:1, and C24OHA were particularly higher in males compared with females in both wild-type and Fabry mice. Similarly, kidney lyso-Gb(3) concentrations were significantly higher in 12-month-old male Fabry mice than in their homozygous female counterparts. However, lyso-Gb(3) was undetectable in wild-type mice of both sexes. α-Galactosidase A activity and mRNA levels in kidney were significantly lower in male wild-type mice compared with female mice. This study shows the sex differences in kidney and urine Gb(3) and kidney lyso-Gb(3) levels in both wild-type and Fabry mice, and it suggests that these male-female differences should be taken into consideration when using murine models for Fabry disease.
authors: Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX, USA.
authors: Brandon
authors: B
authors: Durant
authors: Sabrina
authors: S
authors: Forni
authors: Lawrence
authors: L
authors: Sweetman
authors: Nastry
authors: N
authors: Brignol
authors: Xing-Li
authors: XL
authors: Meng
authors: Elfrida R
authors: ER
authors: Benjamin
authors: Raphael
authors: R
authors: Schiffmann
authors: Jin-Song
authors: JS
authors: Shen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000652:urine; D004195:Disease Models, Animal; D000795:Fabry Disease / Q000235:genetics / Q000652:urine*; D005260:Female; D006801:Humans; D007668:Kidney / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012727:Sex Characteristics; D053719:Tandem Mass Spectrometry / Q000379:methods; D014281:Trihexosylceramides / Q000032:analysis* / Q000652:urine*; D000519:alpha-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D000519:alpha-Galactosidase