B6(Cg)-Lpin1^{tm1c(EUCOMM)Hmgu}/FincJ

Stock number: 032117
Product name: Lpin1 floxed
Research areas: Cardiovascular Research, Metabolism Research, Research Tools

Description

Lpin1^fl mice have exon 7 of the lipin 1 (Lpin1) gene floxed, making these mice useful for studying lipid metabolism, adipocyte differentiation, and skeletal myopathy associated with rhabdomyolysis.

Detailed description

Lpin1^fl floxed mice have loxP sites flanking exon 7 of the lipin 1 (Lpin1) gene. LPIN1 encodes a phosphatidate phosphohydrolase (PAP) enzyme in the triglyceride synthesis pathway that regulates glycerolipid homeostasis and transcription factor activity. It is involved in lipid metabolism gene expression and adipocyte differentiation. Mutations of LPIN1 have been associated with early-onset, recurrent pediatric rhabdomyolysis - a condition in which damage to skeletal myocytes results in substantial buildup of myocellular proteins in the blood. Severe rhabdomyolysis can cause acute kidney failure and may lead to death.

Mice that are homozygous for the Lpin1^fl allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 7 deleted in the Cre-expressing tissues.

When bred to MCK-Cre mice, expressing Cre recombinase in skeletal and cardiac muscle (see Stock Number 006475), resulting mice exhibit a chronic myopathy with ongoing muscle fiber necrosis and regeneration, and accumulation of phosphatidic acid and diacylglycerol. Those mice have abundant, yet abnormal mitochondria and exhibit increased plasma creatine kinase following fasting and exhaustive exercise.

Development

The L1L2_Bact_P cassette was inserted at a position on Chromosome 12 upstream of exon 7 of the lipin 1 (Lpin1) gene. The cassette is composed of a frt site followed by lacZ sequence and a loxP site. This first loxP site is followed by neomycin under the control of the human beta-actin promoter, SV40 polyA, a second frt site and a second loxP site. A third loxP site was inserted downstream of exon 7. The construct, clone HEPD0711_7_B10, was introduced into C57BL/6N-A^tm1Brd-derived JM8A3.N1 embryonic stem (ES) cells, and correctly targeted ES cells were injected into blastocysts. The resulting chimeric males were bred to B6(Cg)-Tyr^c-2J/J female mice (Stock No. 000058). Subsequently these mice were bred to B6.Cg-Tg(ACTFLPe)9205Dym/J mice (Stock No. 005703) to remove the frt-flanked lacZ sequence and neomycin cassette. Resulting Lpin1^fl offspring were bred to C57BL/6J mice (Stock No. 000664). Cryopreserved sperm was sent to The Jackson Laboratory Repository. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Lpin1^{tm1c(EUCOMM)Hmgu}
Name: targeted mutation 1c, Helmholtz Zentrum Muenchen GmbH
MGI accession ID: MGI:6162642
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Lpin^fl
Marker symbol: Lpin1
Marker name: lipin 1
Marker synonyms: Lipin1; mKIAA0188; PAP1
Chromosome: 12
Strain of origin: C57BL/6N-A^tm1Brd
Molecular note: The L1L2_Bact_P cassette was inserted at a position on Chromosome 12 upstream of exon 7 of the gene. The cassette is composed of an FRT site followed by lacZ sequence and a loxP site. This first loxP site is followed by neomycin under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site. A third loxP site was inserted downstream of exon 7. Flp-mediated recombination removed the FRT-flanked neo cassette leaving exon 7 floxed.