RGD Reference Report - A hypomorphic mutation in Lpin1 induces progressively improving neuropathy and lipodystrophy in the rat. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

A hypomorphic mutation in Lpin1 induces progressively improving neuropathy and lipodystrophy in the rat.

Authors: Mul, Joram D  Nadra, Karim  Jagalur, Noorjahan B  Nijman, Isaac J  Toonen, Pim W  Médard, Jean-Jacques  Grès, Sandra  de Bruin, Alain  Han, Gil-Soo  Brouwers, Jos F  Carman, George M  Saulnier-Blache, Jean-Sébastien  Meijer, Dies  Chrast, Roman  Cuppen, Edwin 
Citation: Mul JD, etal., J Biol Chem. 2011 Jul 29;286(30):26781-93. doi: 10.1074/jbc.M110.197947. Epub 2011 Jun 1.
RGD ID: 38599010
Pubmed: PMID:21715287   (View Abstract at PubMed)
PMCID: PMC3143639   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M110.197947   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Lpin1Ratnegative regulation of myelination  IMP  RGD 
Lpin1Ratnegative regulation of phosphatidic acid biosynthetic process  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Lpin1Ratabnormal sciatic nerve morphology  IMP  RGD 
Lpin1m1HubrRatabnormal sciatic nerve morphology  IMP compared to Wild typeRGD 
WI-Lpin1m1HubrRatabnormal sciatic nerve morphology  IMP compared to Wild typeRGD 
Lpin1Ratdysmyelination  IMP  RGD 
Lpin1m1HubrRatdysmyelination  IMP compared to Wild typeRGD 
WI-Lpin1m1HubrRatdysmyelination  IMP compared to Wild typeRGD 
Lpin1Ratincreased cell proliferation  IMP  RGD 
Lpin1m1HubrRatincreased cell proliferation  IMP compared to Wild typeRGD 
WI-Lpin1m1HubrRatincreased cell proliferation  IMP compared to Wild typeRGD 
Lpin1Ratlipodystrophy  IMP  RGD 
Lpin1m1HubrRatlipodystrophy  IMP compared to Wild typeRGD 
WI-Lpin1m1HubrRatlipodystrophy  IMP compared to Wild typeRGD 
Lpin1Ratweight loss  IMP  RGD 
Lpin1m1HubrRatweight loss  IMP compared to Wild type and heterozygousRGD 
WI-Lpin1m1HubrRatweight loss  IMP compared to Wild type and heterozygousRGD 
Objects Annotated

Genes (Rattus norvegicus)
Lpin1  (lipin 1)
Lpin1m1Hubr  (lipin 1; ENU induced mutant 1, Hubr)

Strains
WI-Lpin1m1Hubr  (NA)


Additional Information