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Temporal Ordering of Dynamic Expression Data from Detailed Spatial Expression Maps
Published on: February 9, 2017
Tissue distribution of the murine phosphomannomutases Pmm1 and Pmm2 during brain development
K Cromphout1, L Keldermans, A Snellinx
1Division of Clinical Genetics, Center for Human Genetics, Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium.
Abstract:
The most common type of the congenital disorders of glycosylation, CDG-Ia, is caused by mutations in the human PMM2 gene, reducing phosphomannomutase (PMM) activity. The PMM2 mutations mainly lead to neurological symptoms, while other tissues are only variably affected. Another phosphomannomutase, PMM1, is present at high levels in the brain. This raises the question why PMM1 does not compensate for the reduced PMM2 activity during CDG-Ia pathogenesis. We compared the expression profile of the murine Pmm1 and Pmm2 mRNA and protein in prenatal and postnatal mouse brain at the histological level. We observed a considerable expression of both Pmms in different regions of the embryonic and adult mouse brain. Surprisingly, the expression patterns were largely overlapping. This data indicates that expression differences on the cellular and tissue level are an unlikely explanation for the absence of functional compensation. These results suggest that Pmm1 in vivo does not exert the phosphomannomutase-like activity seen in biochemical assays, but either acts on as yet unidentified specific substrates or fulfils entirely different functions.
Insights
Congenital disorder of glycosylation Ia (CDG-Ia) involves PMM2 gene mutations. Despite PMM1
Area of Science:
- Biochemistry
- Genetics
- Neuroscience
Background:
- Congenital disorders of glycosylation (CDG) are a group of rare genetic diseases.
- CDG-Ia, the most common type, results from mutations in the PMM2 gene, leading to reduced phosphomannomutase (PMM) activity and primarily neurological symptoms.
- PMM1 is highly expressed in the brain, yet its role in compensating for PMM2 deficiency in CDG-Ia is unclear.
Purpose of the Study:
- To investigate why PMM1 does not compensate for reduced PMM2 activity in CDG-Ia.
- To compare the expression patterns of Pmm1 and Pmm2 mRNA and protein in the developing and adult mouse brain.
Main Methods:
- Histological analysis of murine Pmm1 and Pmm2 mRNA and protein expression.
- Comparison of expression profiles in prenatal and postnatal mouse brain regions.
Main Results:
- Both Pmm1 and Pmm2 exhibit considerable expression in various regions of the embryonic and adult mouse brain.
- The expression patterns of Pmm1 and Pmm2 largely overlap across different brain areas and developmental stages.
- Cellular and tissue-level expression differences do not explain the lack of PMM1 compensation in vivo.
Conclusions:
- Overlapping expression patterns suggest that PMM1's lack of compensation in CDG-Ia is not due to tissue distribution.
- PMM1 may not function as a phosphomannomutase in vivo, potentially acting on different substrates or fulfilling alternative roles.
- Further research is needed to elucidate the specific in vivo functions of PMM1.
