Tissue-specific expression of the ABCC6 gene

Area of Science:

• Genetics and Molecular Biology
• Biochemistry
• Medical Genetics

Background:

• The ABCC6 gene encodes multidrug resistance-associated protein 6 (MRP6).
• Mutations in ABCC6 are linked to pseudoxanthoma elasticum (PXE).
• Previous studies suggested primary expression in the liver and kidney, but a wider distribution was also proposed.

Purpose of the Study:

• To investigate the tissue-specific expression pattern of the ABCC6 gene.
• To clarify the expression levels in various mouse tissues and human cell types.

Main Methods:

• Reverse transcription polymerase chain reaction (RT-PCR) was used to analyze ABCC6 mRNA expression in mouse tissues.
• Nested PCR was employed for tissues with initially undetectable expression.
• Subcloning and sequencing were performed on PCR products to identify molecular changes.

Main Results:

• High ABCC6 mRNA levels were detected in the liver, with lower levels in the kidney and small intestine.
• Nested PCR revealed expression in the brain, tongue, stomach, and eye.
• Distinct, smaller PCR products in these tissues indicated aberrant 3' end splicing, leading to premature termination codons.

Conclusions:

• ABCC6 is highly expressed in the liver and kidney, with very low expression in other tissues.
• Aberrant splicing of ABCC6 mRNA occurs in various tissues.
• These findings have implications for PXE mutation detection and support PXE as a primary metabolic disorder.