Mice with an aspartylglucosaminuria mutation similar to humans replicate the pathophysiology in patients

Human Molecular Genetics
A JalankoL Peltonen

Abstract

Aspartyglucosaminuria (AGU) is a lysosomal storage disease with autosomal recessive inheritance that is caused by deficient activity of aspartylglucosaminidase (AGA), a lysosomal enzyme belonging to the newly described enzyme family of N-terminal hydrolases. An AGU mouse model was generated by targeted disruption of the AGA gene designed to mimic closely one human disease mutation. These homozygous mutant mice have no detectable AGA activity and excrete aspartylglucosamine in their urine. Analogously to the human disease, the affected homozygous animals showed storage in lysosomes in all analyzed tissues, including the brain, liver, kidney and skin, and lysosomal storage was already detected in fetuses at 19 days gestation. Electron microscopic studies of brain tissue samples demonstrated lysosomal storage vacuoles in the neurons and glia of the neocortical and cortical regions. Magnetic resonance images (MRI) facilitating monitoring of the brains of living animals indicated cerebral atrophy and hypointensity of the deep gray matter structures of brain-findings similar to those observed in human patients. AGU mice are fertile, and up to 11 months of age their movement and behavior do not differ from their age-matched littermate...Continue Reading

Citations

Aug 23, 2001·Brain Research. Brain Research Reviews·R D'Hooge, P P De Deyn
Feb 28, 2002·Radiology·G Allan JohnsonLaurence W Hedlund
Apr 21, 2001·European Journal of Human Genetics : EJHG·R F KooyA Van Der Linden
Mar 11, 2003·Human Genetics·Reijo Norio
Oct 28, 2019·AJNR. American Journal of Neuroradiology·A TokolaT Autti
Nov 14, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xin ChenSteven J Gray
Nov 26, 1999·Biochimica Et Biophysica Acta·N N Aronson

❮ Previous
Next ❯

Related Concepts

Related Feeds

Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.