Overview

Also Known As:Dgcr^2lox

These floxed mutant mice harbor loxP sites flanking exon 3 of the DiGeorge syndrome critical region gene 8 (Dgcr8) gene and may be useful in generating conditional mutations for studying the role of Dgcr8 in microRNA regulation.

Donating Investigator

Robert Blelloch, University of California, San Francisco

Genetic overview

Genetic Background	Generation

Dgcr8^tm1.1Blel

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Dgcr8	DGCR8, microprocessor complex subunit

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Research Applications

Research Tools
Cell Biology Research
Neurobiology Research

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Details

Detailed Description

Mice homozygous for this Dgcr8^2lox (or Dgcr8^flox) conditional allele are viable and fertile, with loxP sites flanking exon 3 of the Dgcr8 (DiGeorge syndrome critical region gene 8) locus. When bred to mice that express Cre recombinase, the resulting offspring will have the floxed region deleted in cre-expressing tissues. Such a deletion of exon 3 generates a frameshift mutation with multiple downstream premature stop codons resulting in a truncated protein missing the WW protein-protein interaction and RNA-binding domains. This deletion will disrupt Drosha/Dgcr8-dependent cleavage of precursor miRNAs in the nucleus and thus inhibit canonical microRNA biogenesis.

Development

A targeting construct was designed to insert a loxP site upstream of exon 3, and a loxP-flanked CMV-HygroTK selection cassette downstream of exon 3 of the Dgcr8 (DiGeorge syndrome critical region gene 8) locus. This construct was electroporated into (C57BL/6 x 129S4Sv/Jae)-derived V6.5 embryonic stem (ES) cells. Correctly targeted ES cells were then transiently transfected with a Cre recombinase-expressing plasmid. The resulting ES cells with the Dgcr8^2lox (Dgcr8^flox) genotype (CMV-HygroTK selection cassette removed; leaving a single loxP site upstream of exon 3 and a single loxP site downstream of exon 3) were injected into recipient blastocysts. Chimeric mice were bred with C57BL/6NCr inbred mice to generate the Dgcr8^2lox colony. Mutant mice were backcrossed to C57BL/6NCr for eight generations, and thereafter maintained by breeding homozygous mice together for many generations prior to sending to the MMRRC at The Jackson Laboratory Repository. Upon arrival, mice were bred with C57BL/6NJ inbred mice for at least one generation to establish the colony.

Control Suggestions

005304 C57BL/6NJ

Additional Information

Considerations for Choosing Controls

Selected References

Rao PK; Toyama Y; Chiang HR; Gupta S; Bauer M; Medvid R; Reinhardt F; Liao R; Krieger M; Jaenisch R; Lodish HF; Blelloch R. 2009. Loss of cardiac microRNA-mediated regulation leads to dilated cardiomyopathy and heart failure. Circ Res 105(6):585-94PubMed: 19679836 MGI: J:161342

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Genetics

Dgcr8^tm1.1Blel

Allele Symbol: Dgcr8^tm1.1Blel

Allele Name	targeted mutation 1.1, Robert Blelloch
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	Dgcr^2lox
Gene Symbol and Name	Dgcr8, DGCR8, microprocessor complex subunit
Gene Synonym(s)
Strain of Origin	(C57BL/6 x 129S4/SvJae)F1
Chromosome	16
Molecular Note	A loxP site was inserted in intron 2 and a floxed CMV-Hygro selection cassette was inserted in intron 3. ES cells were sequentially targeted so that ES cells carried two mutated alleles. Cre recombinase treatment of these ES cells resulted in two mutant alleles, this one with a floxed exon 3 but lacking the selection cassette and another allele which lacks both exon 3 and the selection cassette.
Mutations Made By	Robert Blelloch, University of California, San Francisco

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Genetics Research
  - Mutagenesis and Transgenesis: Cre-lox System
  - Mutagenesis and Transgenesis
  - Mutagenesis and Transgenesis: transcriptional activation
- Reproductive Biology Research
  - Cre-lox System
- Cre-lox System
  - loxP-flanked Sequences
- Diabetes and Obesity Research
  - loxP
- Developmental Biology Research
  - Cre-lox System
- Cardiovascular Research
  - Cre-lox System
Cell Biology Research
- Transcriptional Regulation
- Post-translational Processing
Neurobiology Research
- Cre-lox System
  - loxP-flanked Sequences

Mammalian Phenotype Terms by Genotype

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

Genotype: Dgcr8^tm1.1Blel/Dgcr8^tm1.1Blel Tg(Ckmm-cre)5Khn/0
involves: 129S4/SvJae * C57BL/6 * FVB

mortality/aging

premature death
- all mice die before 2 months of age and median survival is 31 days

muscle phenotype

decreased ventricle muscle contractility
- at 3 weeks, mice exhibit loss of ventricular function unlike wild-type mice
- at 4 weeks, fractional shortening is reduced in the ventricle compared with wild-type mice

cardiovascular system phenotype

cardiac fibrosis
- in the ventricular wall at 3 weeks

decreased ventricle muscle contractility
- at 4 weeks, fractional shortening is reduced in the ventricle compared with wild-type mice
- at 3 weeks, mice exhibit loss of ventricular function unlike wild-type mice

thin ventricular wall
- in the left and right ventricular wall

enlarged heart

prolonged PR interval

prolonged QRS complex duration
- increased in width

abnormal heart ventricle morphology
- at 4 weeks, mice exhibit increased end-diastolic and end-systolic diameters compared with wild-type mice

growth/size/body region phenotype

enlarged heart

References

Rao PK; Toyama Y; Chiang HR; Gupta S; Bauer M; Medvid R; Reinhardt F; Liao R; Krieger M; Jaenisch R; Lodish HF; Blelloch R. 2009. Loss of cardiac microRNA-mediated regulation leads to dilated cardiomyopathy and heart failure. Circ Res 105(6):585-94PubMed: 19679836 MGI: J:161342

Additional - Dgcr8^tm1.1Blel related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Dgcr8
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the Dgcr^2lox mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #32051 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

The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

General Terms and Conditions

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Dgcr2lox

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Dgcr8tm1.1Blel

Allele Symbol: Dgcr8tm1.1Blel

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Dgcr8tm1.1Blel/Dgcr8tm1.1Blel Tg(Ckmm-cre)5Khn/0involves: 129S4/SvJae * C57BL/6 * FVB

mortality/aging

muscle phenotype

cardiovascular system phenotype

growth/size/body region phenotype

References

Additional - Dgcr8tm1.1Blel 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

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Also Known As:Dgcr^2lox

Dgcr8^tm1.1Blel

Allele Symbol: Dgcr8^tm1.1Blel

Genotype: Dgcr8^tm1.1Blel/Dgcr8^tm1.1Blel Tg(Ckmm-cre)5Khn/0
involves: 129S4/SvJae * C57BL/6 * FVB

Additional - Dgcr8^tm1.1Blel related