B6.Cg-Nr1d1^tm1Ven/LazJ

Stock number: 018447
Product name: Rev-erb-alpha-
Research areas: Developmental Biology Research, Internal/Organ Research, Neurobiology Research, Research Tools

Description

An inserted β-geo fusion protein disrupts the Nr1d1 gene in these Rev-erbAα^-/- KO/reporter mice. Homozygotes exhibit liver steatosis and a delay in cerebellum development. This line may have applications in studies related to circadian clock function, metabolism, and postnatal cerebellar development.

Detailed description

Rev-erbAα^-/- mice have a β-geo cassette replacing part of exon 2, all of exons 3-5, and part of exon 6 of the nuclear receptor subfamily 1, group D, member 1 (Nr1d1) gene, abolishing gene function. Rev-erbAα is a nuclear receptor and transcriptional repressor that regulates circadian clock function, metabolism, and postnatal cerebellar development. Homozygous males are viable and exhibit reduced fertility. Homozygous females have reduced fertility with only 32% producing litters. These mice develop normally until 2 weeks of age, when they exhibit delayed cerebellum development including abnormal Purkinje cells and granule cells, and increased apoptosis of neurons in the internal granule cell layer. Rev-erbAα deletion in these mice also disturbs the circadian rhythm in the liver leading to increased hepatic lipogenesis and a 2-fold increase in hepatic triglyceride content. This liver steatosis is similar to that seen in people who suffer from obesity, diabetes, and metabolic syndrome due to misalignment of fasting/feeding and sleep/wake cycles. lacZ expression is evident during embryogenesis in the heart starting at 10.5 days postcoitus and 1 day later in the developing eye. In the adult expression is seen in many cell types, including brain, liver, skeletal myotubes, cardiocytes, as well as in the smooth muscle layers surrounding the intestine and the uterus.

Development

A targeting vector was designed to replace part of exon 2, all of exons 3-5, and part of exon 6 of the nuclear receptor subfamily 1, group D, member 1 (Nr1d1) gene with a β-geo cassette (a fusion of β-galactosidase and a neomycin resistance cassette). The construct was electroporated into embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to C57BL/6J females. These rev-erbAα^-/- mice were bred to C57BL/6J mice for at least 8 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Nr1d1^tm1Ven
Name: targeted mutation 1, Bjorn Vennstrom
MGI accession ID: MGI:2449852
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Synonyms: Rev-erb-alpha^-
Marker symbol: Nr1d1
Marker name: nuclear receptor subfamily 1, group D, member 1
Marker synonyms: A530070C09Rik; EAR1; ear-1; hRev; REVERBA; rev-erbA(alpha); REV-ERBAALPHA; REVERBalpha; REV-ERBalpha; THRA1; THRAL
Chromosome: 11
Strain of origin: Not Specified
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: lacZ expression is evident during embryogenesis in the heart starting at 10.5 days postcoitus and 1 day later in the developing eye. In the adult expression is seen in many cell types, including brain, liver, skeletal myotubes, cardiocytes, as well as in the smooth muscle layers surrounding the intestine and the uterus.
Molecular note: Part of exon 2, exons 3-5, and part of exon 6 were replaced with a lacZ-neo cassette via homologous recombination. The targeted mutation deletes exons encoding the DNA binding domains. Absence of gene expression was confirmed by Northern blot analysis of midbrain/forbrain and cerebellum RNA from P10 and P13 homozygous mutant animals.