Mucopolysaccharidosis type VII in the developing mouse fetus

Area of Science:

• Biochemistry
• Genetics
• Developmental Biology

Background:

• Mucopolysaccharidosis type VII (MPS VII) is a fatal lysosomal storage disease due to beta-glucuronidase deficiency.
• Hydrops fetalis is a common cause of mortality in MPS VII patients.
• In utero transplantation or gene therapy are potential treatment strategies for MPS VII.

Purpose of the Study:

• Characterize the fetal disease progression in a mouse model of MPS VII.
• Determine the earliest onset of storage lesions in MPS VII fetal mice.
• Establish an optimal window for potential in utero therapeutic interventions.

Main Methods:

• Assessed beta-glucuronidase enzyme activity in tissues of affected and control fetal mice.
• Utilized light and electron microscopy to identify storage lesions in fetal tissues.
• Examined MPS VII mice at various gestational ages (13.5, 15.5, 18.5 days) and at birth.

Main Results:

• No detectable beta-glucuronidase activity was found in MPS VII fetal mice, confirming lack of transplacental enzyme transfer.
• Storage lesions were absent at 13.5 days gestation but appeared in the reticulo-endothelial system by 15.5 days gestation.
• Consistent storage lesions were observed in fetal livers by 18.5 days gestation and in brains at birth.

Conclusions:

• Fetal MPS VII mouse models exhibit a progressive development of storage lesions starting mid-gestation.
• Early prenatal intervention, potentially at 13.5 days gestation, could be effective in preventing disease manifestations.
• This study provides crucial data for evaluating the efficacy of in utero therapies for MPS VII.