Investigation of G72 (DAOA) expression in the human brain

Area of Science:

• Neurogenetics
• Molecular Psychiatry

Background:

• Polymorphisms in the G72/G30 locus are linked to schizophrenia and bipolar disorder.
• The physiological role and expression of G72 protein remain unclear.
• Previous reports suggested G72 activates D-amino acid oxidase (DAO), implicating glutamate dysfunction in schizophrenia, but these findings were not consistently reproduced.

Purpose of the Study:

• To investigate the expression of G72 mRNA and protein in relevant human brain regions.
• To clarify the function of the G72 gene in the context of schizophrenia.

Main Methods:

• Northern blotting and RT-PCR (SYBR-Green, Taqman) were used to detect G72 mRNA.
• Western blotting with custom anti-G72 antibodies was employed to detect G72 protein in human tissues.
• In silico analysis of the G72/G30 locus was performed to understand regulatory elements and transcript stability.

Main Results:

• No significant G72 mRNA levels were detected in various human tissues, cell lines, or post-mortem brain samples using sensitive techniques.
• G72 protein was undetectable in human brain regions, spinal cord, and testis via western blotting.
• In silico analysis indicated low or absent G72 expression and potential transcript lability.

Conclusions:

• Native G72 protein appears to be absent in the analyzed human tissues.
• The lack of detectable G72 expression does not support its role in modulating DAO activity in schizophrenia pathology.
• Further investigation into the G72/30 locus and its significance in schizophrenia is warranted.