He L, Lu XY, Jolly AF, Eldridge AG, Watson SJ, Jackson PK, Barsh GS, Gunn TM.
Spongiform degeneration in mahoganoid mutant mice.
Science. 2003 Jan 31;299(5607):710-2.
PubMed.
This interesting report introduces a new enzyme, Mahogunin, which is a ubiquitin ligase implicated in neuronal metabolism. Through caffeine mutagenesis, a Jackson Lab strain produced a mouse with coat color like that of the spongioform mouse Attractin. They delved into the mouse more deeply to see if similar spongioform vacuolation was taking place. After finding the gene, sequence comparisons then defined the protein as a ring finger Ub ligase.
The ubiquitylation assay is adequate, though the assay time is long. This is a bona fide ligase involved in neuronal Ub metabolism, and specific to the brain tissue. The assertion that there is UBC (E2) selectivity is soft, as only two were tried, at high concentration. Nonetheless it is a reasonable idea in general.
Also suspect is the use of Mgn1/2 deletion constructs rather than substitution mutants. These could be structural mutations, easily. Nonetheless the data is welcome and does not hurt.
Tissue stains show the hippocampus to be the first affected, and the results mimic the Atrn KO mouse very strongly.
The clear next question is:
What is the ubiquitylation substrate of Mgn1/2??
And also,
Does it lie in a pathway with Atrn??
Dissecting this pathway will be critical to understanding the role these proteins have in astrocytosis, vacuolation, and the neuronal cell death prevalent in AD, Canavan's, and Prion disorders.
Someone should also study if drinking coffee will hurt us this way. Eek. That would be harsh.
Comments
Cognia Bioinformatics
This interesting report introduces a new enzyme, Mahogunin, which is a ubiquitin ligase implicated in neuronal metabolism. Through caffeine mutagenesis, a Jackson Lab strain produced a mouse with coat color like that of the spongioform mouse Attractin. They delved into the mouse more deeply to see if similar spongioform vacuolation was taking place. After finding the gene, sequence comparisons then defined the protein as a ring finger Ub ligase.
The ubiquitylation assay is adequate, though the assay time is long. This is a bona fide ligase involved in neuronal Ub metabolism, and specific to the brain tissue. The assertion that there is UBC (E2) selectivity is soft, as only two were tried, at high concentration. Nonetheless it is a reasonable idea in general.
Also suspect is the use of Mgn1/2 deletion constructs rather than substitution mutants. These could be structural mutations, easily. Nonetheless the data is welcome and does not hurt.
Tissue stains show the hippocampus to be the first affected, and the results mimic the Atrn KO mouse very strongly.
The clear next question is:
What is the ubiquitylation substrate of Mgn1/2??
And also,
Does it lie in a pathway with Atrn??
Dissecting this pathway will be critical to understanding the role these proteins have in astrocytosis, vacuolation, and the neuronal cell death prevalent in AD, Canavan's, and Prion disorders.
Someone should also study if drinking coffee will hurt us this way. Eek. That would be harsh.
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