B6-Pnpla3*I148M Mouse
Product Name
B6-Pnpla3*I148M Mouse
Product ID
C001692
Strain Name
C57BL/6JCya-Pnpla3tm1(I148M)/Cya
Backgroud
C57BL/6JCya
When using this mouse strain in a publication, please cite “B6-Pnpla3*I148M Mouse (Catalog C001692) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
Gene Alias
Adpn
NCBI ID
Chromosome
Chr 15
MGI ID
Datasheet
Strain Description
The PNPLA3 gene encodes a triglyceride lipase that mobilizes polyunsaturated fatty acids and promotes the secretion of large very-low-density lipoproteins by the liver. It is mainly expressed in the liver, adipose tissue, and hepatic stellate cells, participating in lipid metabolism, especially triglyceride hydrolysis and lipid droplet remodeling. Its I148M mutation is significantly associated with metabolism-associated fatty liver disease (MASLD), alcoholic liver disease, and liver fibrosis. The I148M mutant, as an inhibitor of PNPLA2/ATGL-mediated lipolysis, disrupts lipid droplet metabolism and promotes hepatic steatosis [1]. PNPLA3 is highly upregulated in a high-carbohydrate diet, and the I148M variant exacerbates the harmful effects of a high-sucrose diet on non-alcoholic fatty liver. Targeted degradation of PNPLA3 I148M through means such as shRNA-mediated gene knockout or siRNA can reduce protein abundance and alleviate steatosis [2-3].
B6-Pnpla3*I148M mice are obtained by introducing the I148M mutation into the mouse Pnpla3 gene using gene editing technology. Homozygous B6-Pnpla3*I148M mice are viable and fertile. This model can be used for research on the disease mechanisms and treatment methods of metabolism-associated fatty liver disease (MASLD), alcoholic liver disease, and liver fibrosis.
Reference
Johnson SM, Bao H, McMahon CE, Chen Y, Burr SD, Anderson AM, Madeyski-Bengtson K, Lindén D, Han X, Liu J. PNPLA3 is a triglyceride lipase that mobilizes polyunsaturated fatty acids to facilitate hepatic secretion of large-sized very low-density lipoprotein. Nat Commun. 2024 Jun 6;15(1):4847.
Mashek DG. Hepatic lipid droplets: A balancing act between energy storage and metabolic dysfunction in NAFLD. Mol Metab. 2021 Aug;50:101115.
Murray JK, Long J, Liu L, Singh S, Pruitt D, Ollmann M, Swearingen E, Hardy M, Homann O, Wu B, Holder JR, Sham K, Herberich B, Lo MC, Dou H, Shkumatov A, Florio M, Rulifson IC. Identification and Optimization of a Minor Allele-Specific siRNA to Prevent PNPLA3 I148M-Driven Nonalcoholic Fatty Liver Disease. Nucleic Acid Ther. 2021 Oct;31(5):324-340.
Strain Strategy
Figure 1. Gene editing strategy of B6-Pnpla3*I148M mice. The p.I148M (ATT to ATG) point mutation was introduced into exon 3 in 5’ homology arm of the targeting vector.
Application Area
Research on the disease mechanisms and treatment methods of metabolism-associated fatty liver disease (MASLD), alcoholic liver disease, liver fibrosis, etc;
Research on PNPLA3 I148M inhibitors.
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