ArticleThe Journal of biological chemistry2011
A hypomorphic mutation in Lpin1 induces progressively improving neuropathy and lipodystrophy in the rat.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Autophagy in Schwann cells: A potential pharmacotherapeutic target in diabetic peripheral neuropathy.World journal of diabetes · 2025Review
- Screening and functional validation of lipid metabolism-related lncRNA-46546 based on the transcriptome analysis of early embryonic muscle tissue in chicken.Animal bioscience · 2023Article
- Lipin1 Alleviates Autophagy Disorder in Sciatic Nerve and Improves Diabetic Peripheral Neuropathy.Molecular neurobiology · 2021Article
- Lipin 1 deficiency causes adult-onset myasthenia with motor neuron dysfunction in humans and neuromuscular junction defects in zebrafish.Theranostics · 2021Article
- A review of phosphatidate phosphatase assays.Journal of lipid research · 2020Review
- Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes.Journal of biomedical science · 2020Review
- Yeast phosphatidic acid phosphatase Pah1 hops and scoots along the membrane phospholipid bilayer.Journal of lipid research · 2020Article
- DDHD1, but Not DDHD2, Suppresses Neurite Outgrowth in SH-SY5Y and PC12 Cells by Regulating Protein Transport From Recycling Endosomes.Frontiers in cell and developmental biology · 2020Article
- The Participation of Regulatory Lipids in Vacuole Homotypic Fusion.Trends in biochemical sciences · 2019Review
- Lipin1 deficiency causes sarcoplasmic reticulum stress and chaperone-responsive myopathy.The EMBO journal · 2019Article
- Normal human adipose tissue functions and differentiation in patients with biallelicJournal of lipid research · 2017Article
- Phosphorylation of Dgk1 Diacylglycerol Kinase by Casein Kinase II Regulates Phosphatidic Acid Production in Saccharomyces cerevisiae.The Journal of biological chemistry · 2016Article
- Redundant roles of the phosphatidate phosphatase family in triacylglycerol synthesis in human adipocytes.Diabetologia · 2016Article
- Article
- Altered Lipid Synthesis by Lack of Yeast Pah1 Phosphatidate Phosphatase Reduces Chronological Life Span.The Journal of biological chemistry · 2015Article
- Phosphorylation regulates the ubiquitin-independent degradation of yeast Pah1 phosphatidate phosphatase by the 20S proteasome.The Journal of biological chemistry · 2015Article
- Yeast Nem1-Spo7 protein phosphatase activity on Pah1 phosphatidate phosphatase is specific for the Pho85-Pho80 protein kinase phosphorylation sites.The Journal of biological chemistry · 2014Article
- Cross-talk phosphorylations by protein kinase C and Pho85p-Pho80p protein kinase regulate Pah1p phosphatidate phosphatase abundance in Saccharomyces cerevisiae.The Journal of biological chemistry · 2014Article
- Phosphatidic acid (PA)-preferring phospholipase A1 regulates mitochondrial dynamics.The Journal of biological chemistry · 2014Article
- Distinct roles of the phosphatidate phosphatases lipin 1 and 2 during adipogenesis and lipid droplet biogenesis in 3T3-L1 cells.The Journal of biological chemistry · 2013Article
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Authors and funding
15 authors at 8 institutions in 4 countries.
Funding
Abstract
The Lpin1 gene encodes the phosphatidate phosphatase (PAP1) enzyme Lipin 1, which plays a critical role in lipid metabolism. In this study we describe the identification and characterization of a rat model with a mutated Lpin1 gene (Lpin1(1Hubr)), generated by N-ethyl-N-nitrosourea mutagenesis. Lpin1(1Hubr) rats are characterized by hindlimb paralysis and mild lipodystrophy that are detectable from the second postnatal week. Sequencing of Lpin1 identified a point mutation in the 5'-end splice site of intron 18 resulting in mis-splicing, a reading frameshift, and a premature stop codon. As this mutation does not induce nonsense-mediated decay, it allows the production of a truncated Lipin 1 protein lacking PAP1 activity. Lpin1(1Hubr) rats developed hypomyelination and mild lipodystrophy rather than the pronounced demyelination and adipocyte defects characteristic of Lpin1(fld/fld) mice, which carry a null allele for Lpin1. Furthermore, biochemical, histological, and molecular analyses revealed that these lesions improve in older Lpin1(1Hubr) rats as compared with young Lpin1(1Hubr) rats and Lpin1(fld/fld) mice. We observed activation of compensatory biochemical pathways substituting for missing PAP1 activity that, in combination with a possible non-enzymatic Lipin 1 function residing outside of its PAP1 domain, may contribute to the less severe phenotypes observed in Lpin1(1Hubr) rats as compared with Lpin1(fld/fld) mice. Although we are cautious in making a direct parallel between the presented rodent model and human disease, our data may provide new insight into the pathogenicity of recently identified human LPIN1 mutations.
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