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Complementation studies in human and feline Niemann-Pick type C disease
K L Somers1, D A Wenger, M A Royals
1Department of Pathology, Colorado State University, Fort Collins, Colorado, 80523, USA. klsomers@lamar.colostate.edu
Molecular Genetics and Metabolism
|March 9, 1999
Summary
Complementation studies indicate the gene causing human Niemann-Pick type C disease (NPC) and a feline NPC model involve the same gene. Cell fusions showed no reversal of the NPC phenotype, confirming genetic similarity.
Area of Science:
- Genetics
- Cell Biology
- Comparative Pathology
Background:
- Niemann-Pick type C (NPC) disease is a rare genetic disorder affecting cholesterol metabolism.
- A feline model of NPC disease has been identified, but its genetic basis relative to human NPC is unknown.
Purpose of the Study:
- To determine if the gene responsible for the major form of human NPC is orthologous to the gene in a feline model of NPC.
- To assess complementation by fusing human and feline NPC fibroblasts.
Main Methods:
- Cell fusion of human and feline Niemann-Pick type C fibroblasts.
- Analysis of multinucleated heterokaryons for NPC phenotype complementation.
- Challenging fused cells with low-density lipoprotein (LDL) and filipin staining to detect unesterified cholesterol accumulation.
Main Results:
- All fused multinucleated cells retained the abnormal filipin staining phenotype characteristic of NPC.
- No reversal of the NPC phenotype was observed in the heterokaryons, indicating a lack of complementation.
- The results suggest the genetic defects in human and feline NPC are related.
Conclusions:
- The gene responsible for the major form of human Niemann-Pick type C disease and the feline NPC model are likely orthologous.
- The underlying genetic defect in both human and feline NPC involves similar genes.
- This finding supports the use of the feline model for studying human Niemann-Pick type C disease mechanisms.