Overview

Also Known As:Rev-erb-alpha-

Estimated Removal of Live Colony date: 26 March 2020.

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.

Donating Investigator

Dr. Bjorn Vennstrom, Karolinska Institute

Mitchell A Lazar, UPENN

Genetic overview

Genetic Background	Generation

Nr1d1^tm1Ven

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter, Null/Knockout)	Nr1d1	nuclear receptor subfamily 1, group D, member 1

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Research Applications

Research Tools
Developmental Biology Research
Internal/Organ Research
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

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.

Expression Data

Expressed Gene	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.

Control Suggestions

Wild-type from the colony

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Chomez P; Neveu I; Mansen A; Kiesler E; Larsson L; Vennstrom B; Arenas E. 2000. Increased cell death and delayed development in the cerebellum of mice lacking the rev-erbA(alpha) orphan receptor. Development 127(7):1489-98PubMed: 10704394 MGI: J:60839

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Genetics

Nr1d1^tm1Ven

Allele Symbol: Nr1d1^tm1Ven

Allele Name	targeted mutation 1, Bjorn Vennstrom
Allele Type	Targeted (Reporter, Null/Knockout)
Allele Synonym(s)	Rev-erb-alpha^-
Gene Symbol and Name	Nr1d1, nuclear receptor subfamily 1, group D, member 1
Gene Synonym(s)
Expressed Gene	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.
Strain of Origin	Not Specified
Chromosome	11
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.
Mutations Made By	Dr. Bjorn Vennstrom, Karolinska Institute

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Research Tools
- Genetics Research
  - Tissue/Cell Markers: hepatocytes
- lacZ Expression
- Diabetes and Obesity Research
  - lacZ
Developmental Biology Research
- Internal/Organ Defects
  - liver
Internal/Organ Research
- Liver Defects
- Adipose Defects
Neurobiology Research
- Circadian Rhythms
- Cerebellar Defects
  - Purkinje cell defect

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Nr1d1^tm1Ven/Nr1d1^tm1Ven
Not Specified

cellular phenotype

abnormal Purkinje cell differentiation
- Purkinje cells show a less elaborate dendritic tree during their differentiation period (P10-P16) and a delayed acquisition of Aldolase C expression pattern, indicating a delay in maturation

reproductive system phenotype

reduced female fertility
- only 32% of matings with fertile males produce normal pregnancies compared to 75% for wild-type

growth/size/body region phenotype

decreased body weight

muscle phenotype

abnormal skeletal muscle fiber type ratio
- the solelus muscle of mutants contains a higher amount of the beta/slow (type I) MyHC isoform than wild-type

increased skeletal muscle fiber size
- type I muscle fibers are twice as large in mutants as in wild-type extensor digitorum longus (EDL), however this is based on a very small sample size

nervous system phenotype

abnormal cerebellar granule cell morphology
- mutants show an increase in granule neuronal apoptosis in the inner granule layer (IGL) at P10, P13, P16, and P19 compared to wild-type, but not in adulthood

abnormal cerebellar molecular layer
- the molecular layer shows a 15% and 17% decrease in thickness in lobules VI-VII and IX-X, respectively, at P16, however the size of the molecular layer is normal by P19

abnormal cerebellum development
- mutants exhibit delayed development of the cerebellum

abnormal cerebellum external granule cell layer morphology
- granule cell progenitors are still proliferating at P16 in the EGL unlike in wild-type where no proliferation is seen at this time, indicating that precursor cell proliferation is extended by 3 days up to P16
- the disappearance of the external granule layer (EGL) is delayed, with mutants having a thicker EGL at P16
- the EGL between lobules VI-VII is thicker than between lobules IX-X at P16 and has more cell layers at P10 and P13

abnormal cerebellum morphology

abnormal Purkinje cell dendrite morphology
- the dendritic trees of Purkinje cells are less elaborate than in wild-type from P10 to P16 but appear normal after P19

abnormal Purkinje cell differentiation
- Purkinje cells show a less elaborate dendritic tree during their differentiation period (P10-P16) and a delayed acquisition of Aldolase C expression pattern, indicating a delay in maturation

The following phenotype relates to a compound genotype created using this strain

Genotype: Nr1d1^tm1Ven/Nr1d1^tm1Ven
B6.Cg-Nr1d1

adipose tissue phenotype

increased adipocyte glucose uptake
- during the day, but not night, in brown adipose tissue

cellular phenotype

increased adipocyte glucose uptake
- during the day, but not night, in brown adipose tissue

homeostasis/metabolism phenotype

abnormal circadian temperature homeostasis
- increased core body temperature and brown adipose tissue during the light phase in cold-exposed mice

decreased susceptibility to induced hypothermia
- cold-exposed mice maintain their body temperature and all survive unlike control mice

increased body temperature
- in brown adipose tissue during the light phase in cold-exposed mice

increased core body temperature
- during the day, but not night, in brown adipose tissue

increased oxygen consumption
- in the brown adipose tissue of cold-exposed mice

mortality/aging

decreased sensitivity to induced morbidity/mortality
- all mice exposed to cold between ZT4 and 10 survive unlike wild-type mice

References

Chomez P; Neveu I; Mansen A; Kiesler E; Larsson L; Vennstrom B; Arenas E. 2000. Increased cell death and delayed development in the cerebellum of mice lacking the rev-erbA(alpha) orphan receptor. Development 127(7):1489-98PubMed: 10704394 MGI: J:60839

Additional References

Welch RD; Billon C; Kameric A; Burris TP; Flaveny CA. 2020. Rev-erbalpha heterozygosity produces a dose-dependent phenotypic advantage in mice. PLoS One 15(5):e0227720PubMed: 32407314 MGI: J:288710

Additional - Nr1d1^tm1Ven related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated MCA:Nr1d1
- Separated PCR:Nr1d1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygotes may be bred together, to wildtype littermates, or C57BL/6J inbred mice (Stock No. 000664) The donating investigator reports only 32% of homozygous females produce litters and males exhibit reduced fertility.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Wild-type
- Wild-type x Heterozygote
Citation
When using the Rev-erb-alpha- mouse strain in a publication, please cite the originating article(s) and include JAX stock #018447 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Nr1d1<tm1Ven>

Related Products and Services

Frozen Mouse Embryo	B6.Cg-Nr1d1<tm1Ven>/LazJ Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.Cg-Nr1d1<tm1Ven>/LazJ Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.Cg-Nr1d1<tm1Ven>/LazJ Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.Cg-Nr1d1<tm1Ven>/LazJ Frozen Embryo	$3373.50

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Also Known As:Rev-erb-alpha-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Nr1d1tm1Ven

Allele Symbol: Nr1d1tm1Ven

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Nr1d1tm1Ven/Nr1d1tm1VenNot Specified

cellular phenotype

reproductive system phenotype

growth/size/body region phenotype

muscle phenotype

nervous system phenotype

Genotype: Nr1d1tm1Ven/Nr1d1tm1VenB6.Cg-Nr1d1

adipose tissue phenotype

cellular phenotype

homeostasis/metabolism phenotype

mortality/aging

References

Additional References

Additional - Nr1d1tm1Ven related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Nr1d1^tm1Ven

Allele Symbol: Nr1d1^tm1Ven

Genotype: Nr1d1^tm1Ven/Nr1d1^tm1Ven
Not Specified

Genotype: Nr1d1^tm1Ven/Nr1d1^tm1Ven
B6.Cg-Nr1d1

Additional - Nr1d1^tm1Ven related