Overview

The GFP reporter inserted downstream of the Setd5 promoter eliminates Setd5 transcription (creating a null allele) and provides a reporter for Setd5 expression. SETD5 (SET domain-containing protein 5) is involved in epigenetic repression of gene expression.

Donating Investigator

Mark A. Magnuson, Vanderbilt University School of Medicine

Genetic overview

Genetic Background	Generation

Setd5^tm1.1Mgn

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter)	Setd5	SET domain containing 5

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Research Applications

Research Tools

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Details

Detailed Description

Heterozygous mice harboring the Setd5.GFP reporter are viable and fertile. Mice homozygous for the mutation are not viable. Insertion of the GFP reporter downstream of the Setd5 promoter eliminates Setd5 transcription (creating a null allele) and provides a reporter for Setd5 gene expression. Setd5 is located upstream of Rosa26 and is transcribed in the opposite orientation. SETD5 (SET domain-containing protein 5) is involved in epigenetic repression of gene expression.

Development

Using the ROSA26^LCA or Loxed Cassette Acceptor allele (Gt(ROSA)26Sor^tm1Mgn), which contains a loxP-flanked (lox71, lox2272) selection cassette in the ROSA26 promoter, a donor cassette is inserted into the acceptor allele via recombinase mediated cassette exchange (RMCE). The donor cassette or signaling sentinel construct includes an FRT-flanked pgk-hygromycin and a GFP-SV40 polyA reporter sequence. The GFP reporter inserted into exon1 of the Setd5 gene, which is located upstream of the Rosa26 exon 1 and is transcribed in the opposite orientation. The construct was electroporated into 129S6/SvEvTac-derived TL1 ES cells. Chimeric mice were bred with B6;SJL-Tg(ACTFLPe)9205Dym/J transgenic mice to delete the pgk-hygromycin cassette. The donating investigator reported that the mice were backcrossed to CD-1 mice for 4 generations prior to sending to MMRRC at JAX. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice for at least one generation to establish the colony.

Expression Data

Expressed Gene	GFP, Green Fluorescent Protein,
Site of Expression

Control Suggestions

Approximate Controls

Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Osipovich AB; Gangula R; Vianna PG; Magnuson MA. 2016. Setd5 is essential for mammalian development and the co-transcriptional regulation of histone acetylation. Development 143(24):4595-4607PubMed: 27864380 MGI: J:237500

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Genetics

Setd5^tm1.1Mgn

Allele Symbol: Setd5^tm1.1Mgn

Allele Name	targeted mutation 1.1, Mark Magnuson
Allele Type	Targeted (Reporter)
Allele Synonym(s)	Setd5^GFP
Gene Symbol and Name	Setd5, SET domain containing 5
Gene Synonym(s)
Expressed Gene	GFP, Green Fluorescent Protein,
Strain of Origin	129S6/SvEvTac
Chromosome	6
Molecular Note	The pRosa26.Ex1.Setd5GFP exchange vector was made on a backbone of a basal Rosa26 exchange vector which contains a 5.166 kb sequence from the Rosa26 locus, Lox71/Lox2272 sites, and flrted (flanked by FRT) Pgk-Hygro selection cassette that is used for positive selection after RMCE. A GFP-SV40 polyA sequence was inserted into exon 1 of the Setd5 gene which is located upstream of the Rosa26 exon 1 and is transcribed in the opposite orientation. Gene targeting and RMCE was performed in mESCs derived from 129S6 mice. The chimeric mice were crossed with Flpe mice to remove the hygromycin resistance gene.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Genetics Research
- Cell Biology Research
- Fluorescent Proteins

Mammalian Phenotype Terms by Genotype

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

Genotype: Setd5^tm1.1Mgn/Setd5^tm1.1Mgn
involves: 129S6/SvEvTac * CD-1

cardiovascular system phenotype

abnormal vitelline vasculature morphology
- pale yolk sac with fewer blood vessels at age E9.5

hemorrhage
- widespread hemorrhage at age E10.5

abnormal myocardium layer morphology
- thin myocardium
- no contact with endocardium
- at age E9.5
- large gap with pericardium

abnormal vascular development
- lack of or severely reduced cardiac myosin heavy chain expression in dorsal aorta at age E9.5

pericardial effusion
- up to age E10.5

enlarged heart
- swollen hearts at age E9.5

abnormal myocardial trabeculae morphology
- reduced trabeculation in the existing single ventricle at age E9.5

disorganized yolk sac vascular plexus
- at age E9.5

abnormal placental labyrinth vasculature morphology
- lack of embryonic blood vessels contained (only maternal blood vessels with mature erythrocytes) at age E9.5

abnormal heart morphology
- no beating heart in around 50% of embryos at age E9.5

abnormal vascular plexus formation
- abnormally dilated capillary yolk sac plexus at age E9.5

cellular phenotype

increased embryonic tissue cell apoptosis
- apoptotic cell number increase from 4% to 25% at age E9.5 according to activated Caspase 3 measurements

embryo phenotype

embryonic growth retardation
- smaller and fewer somites at age E9.5, often showing lack of neural tube closure
- underdeveloped at age E10.5

abnormal tail bud morphology
- tail effusions (swelling due to fluid buildup) up to age E10.5

abnormal somite development
- lack of or severely reduced cardiac myosin heavy chain expression in somites at age E9.5
- fewer somites at age E9.5

increased embryonic tissue cell apoptosis
- apoptotic cell number increase from 4% to 25% at age E9.5 according to activated Caspase 3 measurements

abnormal placenta labyrinth morphology
- significantly thinner at age E9.5

disorganized yolk sac vascular plexus
- at age E9.5

abnormal placental labyrinth vasculature morphology
- lack of embryonic blood vessels contained (only maternal blood vessels with mature erythrocytes) at age E9.5

decreased embryo size
- at ages E9.5 and E10.5

abnormal vitelline vasculature morphology
- pale yolk sac with fewer blood vessels at age E9.5

abnormal placenta morphology
- embryonic blood vessels remain in chorioallantoic region, did not invade labyrinthine layer, at age E9.5

growth/size/body region phenotype

decreased embryo size
- at ages E9.5 and E10.5

embryonic growth retardation
- smaller and fewer somites at age E9.5, often showing lack of neural tube closure
- underdeveloped at age E10.5

enlarged heart
- swollen hearts at age E9.5

homeostasis/metabolism phenotype

pericardial effusion
- up to age E10.5

limbs/digits/tail phenotype

abnormal tail bud morphology
- tail effusions (swelling due to fluid buildup) up to age E10.5

mammalian phenotype

hematopoietic system phenotype
- Normal - normal definitive hematopoiesis at age E9.5 according to Itga2b expression

mortality/aging

embryonic lethality during organogenesis, complete penetrance
- no viable embryos beyond age E10.5

muscle phenotype

abnormal myocardium layer morphology
- large gap with pericardium
- at age E9.5
- no contact with endocardium
- thin myocardium

abnormal myocardial trabeculae morphology
- reduced trabeculation in the existing single ventricle at age E9.5

References

Osipovich AB; Gangula R; Vianna PG; Magnuson MA. 2016. Setd5 is essential for mammalian development and the co-transcriptional regulation of histone acetylation. Development 143(24):4595-4607PubMed: 27864380 MGI: J:237500

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Setd5
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation are not viable.
- Additional Breeding and Husbandry Support
Citation
When using the STOCK Setd5^tm1.1Mgn/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36985 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

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Setd5tm1.1Mgn

Allele Symbol: Setd5tm1.1Mgn

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Setd5tm1.1Mgn/Setd5tm1.1Mgninvolves: 129S6/SvEvTac * CD-1

cardiovascular system phenotype

cellular phenotype

embryo phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

limbs/digits/tail phenotype

mammalian phenotype

mortality/aging

muscle phenotype

References

Genotyping Protocols

Breeding Considerations

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

Setd5^tm1.1Mgn

Allele Symbol: Setd5^tm1.1Mgn

Genotype: Setd5^tm1.1Mgn/Setd5^tm1.1Mgn
involves: 129S6/SvEvTac * CD-1