Aldolase B Deficient Mice Are Characterized by Hepatic Nucleotide Sugar Abnormalities

Area of Science:

• Biochemistry
• Genetics
• Metabolic Disorders

Background:

• Hereditary fructose intolerance (HFI) causes liver damage and impaired N-linked glycosylation due to mannose phosphate isomerase (MPI) defects.
• Mannose treatment is effective for MPI-CDG, another condition with liver damage and MPI impairment.

Purpose of the Study:

• To investigate hepatic nucleotide sugar levels in a mouse model of HFI.
• To assess the impact of mannose supplementation on hepatic nucleotide sugar levels and liver fat in HFI mice.

Main Methods:

• Aldolase B deficient (Aldob-/-) mice were administered 5% mannose in drinking water for four weeks.
• Hepatic nucleotide sugar levels and liver fat were analyzed and compared to control Aldob-/- and wildtype mice.

Main Results:

• Aldob-/- mice exhibited lower hepatic GDP-mannose and GDP-fucose, consistent with impaired glycosylation.
• Abnormal levels of other hepatic nucleotide sugars (UDP-glucuronic acid, UDP-xylose, CMP-N-acetyl-beta-neuraminic acid, CDP-ribitol) were observed.
• Mannose treatment did not restore GDP-mannose levels or affect liver fat accumulation.

Conclusions:

• HFI mouse models display significant hepatic nucleotide sugar abnormalities.
• Mannose supplementation did not ameliorate these biochemical alterations or liver steatosis.
• Further studies are required to elucidate the mechanisms behind HFI's nucleotide sugar pattern and liver fat accumulation.