Overview

Also Known As:CAG-Z-FUS^WT-IRES-EGFP transgenic line 629 [CAG-Z-FUS^WT (629)]

The CAG-Z-FUS^WT-IRES-EGFP transgenic line 629 [or CAG-Z-FUS^WT (629)] has widespread expression of lacZ, that is replaced by expression of wildtype human fused in sarcoma protein (huFUS^WT) and EGFP fluorescence following exposure to Cre recombinase. The Cre recombinase-inducible expression of huFUS^WT, along with similarly designed transgenic mice harboring the FUS^R521G mutant isoform (Stock No. 028021), is useful in studying FUS-linked juvenile amyotrophic lateral sclerosis (ALS; Lou Gehrig's Disease), and the neurodegenerative disorder frontotemporal lobar degeneration (FTLD).

Donating Investigator

Gang Yu, University of Texas Southwestern Medical Center at Dallas

Genetic overview

Genetic Background	Generation

Tg(CAG-lacZ,-FUS,-EGFP)629Gyu

Allele Type
Transgenic (Conditional ready (e.g. floxed), Reporter, Inserted expressed sequence, Humanized sequence)

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Research Applications

Developmental Biology Research
Neurobiology Research
Research Tools
Cell Biology Research
Cancer Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Nucleo-cytoplasmic shuttling of fused in sarcoma (FUS) occurs by a nuclear localization signal (NLS). The majority of clinical amyotrophic lateral sclerosis (ALS; Lou Gehrig's Disease) and frontotemporal lobar degeneration (FTLD)-associated FUS mutations occur in its C-terminal NLS sequence. Overexpression of wildtype FUS protein can be pathogenic in human patients as well.

CAG-Z-FUS^WT-IRES-EGFP transgenic line 629 (simply called CAG-Z-FUS^WT (629)) has a floxed-lacZ gene preventing transcription of the downstream bicistronic sequences; a wildtype human fused in sarcoma protein (huFUS^WT) and EGFP. Prior to Cre recombinase exposure, lacZ expression is directed to widespread tissues by the CAG promoter, and no expression of huFUS^WT or EGFP is observed. When bred to mice that express Cre recombinase, the resulting offspring will have the floxed-lacZ deleted in the cre-expressing tissues; resulting in expression of huFUS^WT and EGFP fluorescence in cre-expressing tissues (and continued lacZ expression in other tissues).

Mice hemizygous for the CAG-Z-FUS^WT transgene are viable and fertile, born at normal Mendelian ratios, and have no reported phenotypic abnormalities. To date (September 2015), it has not been attempted to make this strain homozygous.

When CAG-Z-FUS^WT (629) are bred to C57BL/6-congenic Meox2^Cre knock-in animals (Stock No. 003755), germline deletion of floxed-lacZ generates the CAG-FUS^WT-IRES-EGFP genotype (simply called CAG-FUS^WT). Mice hemizygous for the CAG-FUS^WT transgene and heterozygous for Meox2^Cre (Tg/+ , +/Cre) have global overexpression of low levels of huFUS^WT, resulting in severe deficits in motor function, denervation of the neuromuscular junctions (NMJs), muscle atrophy, neuroinflammation and early lethality (none survive to adulthood; nearly 100% die by postnatal day 30). The level of huFUS^WT expression was similar to that of endogenous mouse FUS, resulting in ~2-fold expression levels of total FUS (huFUS^WT + mouse FUS) compared to control mice.

In addition, both CAG-FUS^R521G (Stock No. 028021 with germline deletion of floxed-lacZ) and CAG-FUS^WT transgenic mouse models exhibit no overt motor neuron loss, no apparent ubiquitin-positive aggregation and no mislocalization of FUS in neurons and glia. Transcriptomic analysis of spinal cords revealed that the gene expression pattern is altered in CAG-FUS^WT mice, but not significantly altered in CAG-FUS^R521G mice. The CAG-FUS^WT and CAG-FUS^R521G animals display some characteristics of adult ALS. However, the onset of phenotype in the mouse models is earlier, more closely reflecting FUS-linked juvenile ALS.

Development

The CAG-Z-FUS^WT-IRES-EGFP transgene was created by Dr. Gang Yu (University of Texas Southwestern Medical Center at Dallas). The transgene was designed with (from 5' to 3') the CMV-IE enhancer/chicken beta-actin hybrid promoter (CAG), a loxP site, the β-galactosidase gene (lacZ) with nuclear translocation signal and triple polyadenylation sequence, a second loxP site, a cDNA sequence encoding the wildtype human fused in sarcoma protein (huFUS^WT), an internal ribosome entry site sequence (IRES), the enhanced green fluorescent protein gene (EGFP) and a polyadenylation sequence. The ~13.2 kbp construct was injected into fertilized oocytes from C57BL/6J female mice. Transgenic founders were bred to C57BL/6J animals for germline transmission. CAG-Z-FUS^WT-IRES-EGFP founder line 629 (simply called CAG-Z-FUS^WT (629)) was identified with single-to-very low copies of the transgene at a single insertion site. CAG-Z-FUS^WT (629) was backcrossed to C57BL/6J for at least 13 generations prior to sending to The Jackson Laboratory Repository in 2016. Upon arrival, males were used to cryopreserve sperm. To establish our living colony, an aliquot of the frozen sperm was used to fertilize oocytes from C57BL/6J inbred females (Stock No. 000664).

Of note, the donating investigator reports that, at least once during backcrossing, a heterozygous female was bred to a C57BL/6J inbred male (thus the Y chromosome of the congenic strain is of C57BL/6J origin).

Expression Data

Expressed Gene	GFP, Green Fluorescent Protein,
Expressed Gene	lacZ, beta-galactosidase, E. coli
Expressed Gene	FUS, fused in sarcoma , human
Site of Expression	Prior to cre recombination lacZ is widely expressed; the human wildtype fused in sarcoma protein and EGFP are expressed only after cre recombination in cre-expressing tissues.

Control Suggestions

Noncarrier

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Sephton CF; Tang AA; Kulkarni A; West J; Brooks M; Stubblefield JJ; Liu Y; Zhang MQ; Green CB; Huber KM; Huang EJ; Herz J; Yu G. 2014. Activity-dependent FUS dysregulation disrupts synaptic homeostasis. Proc Natl Acad Sci U S A 111(44):E4769-78PubMed: 25324524 MGI: J:216672

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Genetics

Tg(CAG-lacZ,-FUS,-EGFP)629Gyu

Allele Symbol: Tg(CAG-lacZ,-FUS,-EGFP)629Gyu

Allele Name	transgene insertion 629, Gang Yu
Allele Type	Transgenic (Conditional ready (e.g. floxed), Reporter, Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)
Gene Symbol and Name	Tg(CAG-lacZ,-FUS,-EGFP)629Gyu, transgene insertion 629, Gang Yu
Gene Synonym(s)
Promoter	CAG, CMV-IE enhancer/chicken beta-actin/rabbit beta-globin hybrid promoter,
Expressed Gene	GFP, Green Fluorescent Protein,
Expressed Gene	lacZ, beta-galactosidase, E. coli
Expressed Gene	FUS, fused in sarcoma , human
Site of Expression	Prior to cre recombination lacZ is widely expressed; the human wildtype fused in sarcoma protein and EGFP are expressed only after cre recombination in cre-expressing tissues.
Strain of Origin	C57BL/6J
Chromosome	UN
Molecular Note	This transgene consists of the cytomegalovirus immediate early enhancer-chicken beta-actin hybrid (CAG) promoter, a floxed lacZ gene, wild-type human FUS cDNA, IRES, and EGFP coding sequences. Cre-excision of the loxP flanked lacZ DNA sequence allows for translation of FUS and EGFP. Two lines were generated: 629 and 638. Line 629 was chosen as a representative line.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Developmental Biology Research
- Postnatal Lethality
Neurobiology Research
- Fluorescent protein expression in neural tissue
- Ataxia (Movement) Defects
- Cre-lox System
  - loxP-flanked Sequences
- Neurodegeneration
- Amyotrophic Lateral Sclerosis (ALS)
- Neuromuscular defects
- lacZ expression in neural tissue
Research Tools
- lacZ Expression
- Fluorescent Proteins
- Developmental Biology Research
  - Cre-lox System
- Genetics Research
  - Mutagenesis and Transgenesis: Cre-lox System
  - Tissue/Cell Markers: Cre-lox System
- Neurobiology Research
- Cre-lox System
  - loxP-flanked Sequences
Cell Biology Research
- Transcriptional Regulation
Cancer Research
- Cre-lox System
  - loxP-flanked Sequences

Mammalian Phenotype Terms by Genotype

References

Sephton CF; Tang AA; Kulkarni A; West J; Brooks M; Stubblefield JJ; Liu Y; Zhang MQ; Green CB; Huber KM; Huang EJ; Herz J; Yu G. 2014. Activity-dependent FUS dysregulation disrupts synaptic homeostasis. Proc Natl Acad Sci U S A 111(44):E4769-78PubMed: 25324524 MGI: J:216672

Additional - Tg(CAG-lacZ,-FUS,-EGFP)629Gyu related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Tg(CAG-lacZ,-FUS-EGFP)Gyu-alternate2
- Sanger sequencing:Tg(CAG-lacZ,-FUS*R521G,-EGFP)673Gyu-alternate1
- Probe:Fluorescent Proteins (Generic GFP)
- Standard PCR:Tg(FUS)
- Standard PCR:Generic LacZ Melt Curve Analysis
- Probe:Generic LacZ Probe
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, transgenic mice may be bred with wildtype (noncarrier) mice from the colony or with C57BL/6J inbred mice (Stock No. 000664). To date (September 2015), it has not been attempted to make this strain homozygous.
- Additional Breeding and Husbandry Support
Citation
When using the CAG-Z-FUS^WT-IRES-EGFP transgenic line 629 [CAG-Z-FUS^WT (629)] mouse strain in a publication, please cite the originating article(s) and include JAX stock #027898 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
	Hemizygous or Non Carrier for Tg(CAG-lacZ,-FUS,-EGFP)629Gyu

Related Products and Services

Frozen Mouse Embryo	C57BL/6J-Tg(CAG-lacZ -FUS -EGFP)629Gyu/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	C57BL/6J-Tg(CAG-lacZ -FUS -EGFP)629Gyu/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	C57BL/6J-Tg(CAG-lacZ -FUS -EGFP)629Gyu/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	C57BL/6J-Tg(CAG-lacZ -FUS -EGFP)629Gyu/J Frozen Embryo	$3373.50

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Also Known As:CAG-Z-FUSWT-IRES-EGFP transgenic line 629 [CAG-Z-FUSWT (629)]

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Tg(CAG-lacZ,-FUS,-EGFP)629Gyu

Allele Symbol: Tg(CAG-lacZ,-FUS,-EGFP)629Gyu

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

References

Additional - Tg(CAG-lacZ,-FUS,-EGFP)629Gyu related

Genotyping Protocols

Breeding Considerations

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

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As:CAG-Z-FUS^WT-IRES-EGFP transgenic line 629 [CAG-Z-FUS^WT (629)]