Phenotypes Associated with This Genotype

Genotype
MGI:2183938

• Allelic Composition: Gla^tm1Kul/Y
• Genetic Background: involves: 129S4/SvJae * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Lipid inclusions with electron-dense concentric lamellar structures in the lysosomes of Gla^tm1Kul/Y renal tubular cells

renal/urinary system

abnormal kidney morphology ( J:39394 )

♂ • electron microscopy reveales concentric lamellar incusions within lysosomes of renal tubular cells

♂ • marked accumulation of ceramidetrihexoside in the liver and kidneys

♂ • mice otherwise appear healthy up to 10-14 weeks of age

liver/biliary system

abnormal liver morphology ( J:39394 )

♂ • marked accumulation of ceramidetrihexoside in the liver and kidneys

cellular

abnormal cell morphology ( J:39394 )

♂ • accumulation of material containing terminal alpha-galactosyl residues in cultured embryonic fibroblasts

cardiovascular system

dilated aorta ( J:187258 )

♂ • increase in the aortic diameter during diastole indicating ascending aortic dilation, however it is not associated with aortic valvular regurgitation

heart left ventricle hypertrophy ( J:187258 )

♂ • increase in left ventricular mass at 4 months of age when normalized to body weight

increased heart weight ( J:187258 )

♂ • heart weight is increased, when normalized to body weight or tibial weight

abnormal cardiovascular system physiology ( J:187258 )

♂ • mutant males exhibit mild diastolic left ventricular dysfunction as indicated by a decrease in the maximal diastolic velocity of the mitral annulus, without change in the isovolumic relaxation time

♂ • however, global left ventricular systolic function is similar to wild-type mice

♂ • treatment with a single dose of agalsidase-beta, a type of enzyme replacement therapy, does not affect the left ventricular hypertrophy, function or heart rate, but improves the mRNA signals of early cardiac remodeling

decreased heart rate ( J:187258 )

♂ • heart rate is slower in 4 month old males

prolonged RR interval ( J:187258 )

♂ • however, no differences in PQ, QRS, or corrected QT intervals

♂ • males exhibit prolonged RR intervals

irregular heartbeat ( J:187258 )

♂ • premature atrial contractions are more frequently observed in mutant males than in wild-type males

decreased systemic arterial systolic blood pressure ( J:187258 )

♂ • lower systolic blood pressure in males than in wild-type males

cardiomyopathy ( J:187258 )

♂ • mild hypertrophic cardiomyopathy

muscle

heart left ventricle hypertrophy ( J:187258 )

♂ • increase in left ventricular mass at 4 months of age when normalized to body weight

cardiomyopathy ( J:187258 )

♂ • mild hypertrophic cardiomyopathy

growth/size/body

heart left ventricle hypertrophy ( J:187258 )

♂ • increase in left ventricular mass at 4 months of age when normalized to body weight

increased heart weight ( J:187258 )

♂ • heart weight is increased, when normalized to body weight or tibial weight

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Fabry disease		DOID:14499	OMIM:301500	J:39394 , J:187258