Overview

The ubiquitous CrT knockout allele (CrT^-) has a deletion of the exons encoding the 2nd-4th transmembrane domain of the creatine transporter gene on the X chromosome. These mice may be useful for studying creatine transport and human X-linked creatine deficiency syndrome, mental retardation, autism, and speech, language, cognitive, and memory disorders.

Donating Investigator

Joseph F Clark, University of Cincinnati

Genetic overview

Genetic Background	Generation

Slc6a8^tm1.2Clar

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Slc6a8	solute carrier family 6 (neurotransmitter transporter, creatine), member 8

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Research Applications

Neurobiology Research
Cell Biology Research
Developmental Biology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The ubiquitous CrT knockout allele (CrT^-) has a deletion of the exons encoding the 2nd-4th transmembrane domain of the creatine transporter gene on the X chromosome. Heterozygous females (CrT^+/-) are viable and fertile with no observed abnormalities. Hemizygous males (CrT^-/Y) do not breed (perhaps due to behavioral/cognitive phenotype; fertility is unknown). No homozygous females have been generated to date (January 2013). Males hemizygous for the pan deletion (CrT^-/Y) lack creatine in brain and muscle, have significant creatine reductions in other tissues (including heart and testis), and exhibit learning and memory deficits resembling human X-linked creatine deficiency syndrome.

Of note, the donating investigator also sent the CrT^flox conditional mice (floxed exons 2-4) to The Jackson Laboratory Repository as Stock No. 020642.

Development

A targeting vector was designed by Dr. Joseph F. Clark (University of Cincinnati) to insert a loxP site upstream of exon 2, and an frt-flanked neo cassette and second loxP site downstream of exon 4 of the creatine transporter gene (CrT; Slc6a8) on the X chromosome. The construct was electroporated into C57BL/6-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient MF-1 blastocysts. Chimeric males were bred with C57BL/6J females to generate the conditional founder mice. To remove the frt-flanked neo cassette, mice were bred with the germline FLP deleter strain (B6;SJL-Tg(ACTFLPe)9205Dym/J; Stock No. 003800). Offspring with the CrT^flox allele (loxP site upstream of exon 1, and a single frt site and second loxP site downstream of exon 4) were obtained. The CrT^flox mice were bred to C57BL/6J wildtype mice for several generations (and the FLP transgene was removed) prior to sending to The Jackson Laboratory Repository in 2013 as Stock No. 020642. Upon arrival, some CrT^flox mice were bred to animals expressing Cre recombinase in the germline (B6.Sox2Cre; Stock No. 008454) to remove floxed exons 2-4. Offspring with the ubiquitous CrT knockout allele (CrT^-) were established. Heterozygous females were bred to C57BL/6J wildtype males to remove the Sox2Cre transgene. The CrT^- colony was then maintained by breeding heterozygous females with wildtype males from the colony or with C57BL/6J inbred males.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Skelton MR; Schaefer TL; Graham DL; Degrauw TJ; Clark JF; Williams MT; Vorhees CV. 2011. Creatine transporter (CrT; Slc6a8) knockout mice as a model of human CrT deficiency. PLoS One 6(1):e16187PubMed: 21249153 MGI: J:169472
Kurosawa Y; Degrauw TJ; Lindquist DM; Blanco VM; Pyne-Geithman GJ; Daikoku T; Chambers JB; Benoit SC; Clark JF. 2012. Cyclocreatine treatment improves cognition in mice with creatine transporter deficiency. J Clin Invest 122(8):2837-46PubMed: 22751104 MGI: J:190081

View All References

Genetics

Slc6a8^tm1.2Clar

Allele Symbol: Slc6a8^tm1.2Clar

Allele Name	targeted mutation 1.2, Joseph Clark
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Slc6a8^tm1.2Clar; targeted mutation 1.2, Joseph Clark
Gene Symbol and Name	Slc6a8, solute carrier family 6 (neurotransmitter transporter, creatine), member 8
Gene Synonym(s)	creatine transporter; CTR5; CHOT1; CRT; CRTR; Creat; AA589632; CHT1; CT1; expressed sequence AA589632; Creat; CCDS1
Strain of Origin	C57BL/6
Chromosome	X
Molecular Note	Cre-mediated recombination of Slc6a8^tm1.1Clar removed exons 2, 3, and 4.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

creatine transporter deficiency

Research Areas By Phenotype

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

Neurobiology Research
- Channel and Transporter Defects
  - sodium
- Behavioral and Learning Defects
- Neurotransmitter Receptor and Synaptic Vesicle Defects
- Neurodevelopmental Defects
  - Autism
Cell Biology Research
- Channel and Transporter Defects
  - sodium
- Signal Transduction
Developmental Biology Research
- Neurodevelopmental Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: Slc6a8^tm1.2Clar/Y
involves: BALB/cJ * C57BL/6 * C57BL/6J * SJL

behavior/neurological phenotype

abnormal short term object recognition memory
- mice spend less time attending a novel object in a short-term novel object recognition test compared with wild-type mice

abnormal spatial learning
- mice exhibit longer latency to finding a visible platform in a Morris water maze likely due to decreased swim speed compared with wild-type mice

hyperactivity
- mice exhibit an increase in activity along the periphery of a novel environment compared with wild-type mice

hypoactivity
- during the first 5 minutes in a novel environment

impaired contextual conditioning behavior
- following contextual fear conditioning, mice exhibit reduced freezing compared with wild-type mice
- Normal - however, cued fear conditioning is normal

impaired swimming
- mice exhibit longer latency to finding a visible platform in a Morris water maze likely due to decreased swim speed compared with wild-type mice

mammalian phenotype

behavior/neurological phenotype
- Normal - mice exhibit normal rearing, social preference, acoustic startle, and prepulse inhibition

nervous system phenotype

increased serotonin level
- in the prefrontal cortex, hippocampus, and neostriatum

growth/size/body region phenotype

decreased body weight

homeostasis/metabolism phenotype

decreased circulating creatine level

decreased creatine level
- Normal - however, kidney levels are normal
- in the brain, muscle, heart, testes, and serum

increased serotonin level
- in the prefrontal cortex, hippocampus, and neostriatum

References

Skelton MR; Schaefer TL; Graham DL; Degrauw TJ; Clark JF; Williams MT; Vorhees CV. 2011. Creatine transporter (CrT; Slc6a8) knockout mice as a model of human CrT deficiency. PLoS One 6(1):e16187PubMed: 21249153 MGI: J:169472
Kurosawa Y; Degrauw TJ; Lindquist DM; Blanco VM; Pyne-Geithman GJ; Daikoku T; Chambers JB; Benoit SC; Clark JF. 2012. Cyclocreatine treatment improves cognition in mice with creatine transporter deficiency. J Clin Invest 122(8):2837-46PubMed: 22751104 MGI: J:190081

Additional - Slc6a8^tm1.2Clar related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Probe:Generic Cre Probe
- Probe:Generic FLP
- Standard PCR:Slc6a8-Alternate 1
- Standard PCR:Tg(ACTFLPe)
- Standard PCR:Tg(ACTFLPe)
- Standard PCR:Generic Neo
- Probe:Generic Neo
- Genotyping resources and troubleshooting
Breeding Considerations

The targeted mutation is on the X chromosome. Heterozygous females have no reported breeding problems. Hemizygous males do not breed (perhaps due to behavioral/cognitive phenotype; fertility is unknown). When maintaining a live colony, heterozygous females are bred with wildtype males from the colony or with C57BL/6J inbred males (Stock No. 000664).
- Additional Breeding and Husbandry Support
Citation
When using the B6(Cg)-Slc6a8^tm1.2Clar/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #021072 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
	X linked Heterozygous females and wildtype males for Slc6a8<tm1.2Clar>

Related Products and Services

Frozen Mouse Embryo	B6(Cg)-Slc6a8<tm1.2Clar>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6(Cg)-Slc6a8<tm1.2Clar>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6(Cg)-Slc6a8<tm1.2Clar>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6(Cg)-Slc6a8<tm1.2Clar>/J 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.

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Questions about Terms of Use

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Licensing Information

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Slc6a8tm1.2Clar

Allele Symbol: Slc6a8tm1.2Clar

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Slc6a8tm1.2Clar/Yinvolves: BALB/cJ * C57BL/6 * C57BL/6J * SJL

behavior/neurological phenotype

mammalian phenotype

nervous system phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

References

Additional - Slc6a8tm1.2Clar 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

Slc6a8^tm1.2Clar

Allele Symbol: Slc6a8^tm1.2Clar

Genotype: Slc6a8^tm1.2Clar/Y
involves: BALB/cJ * C57BL/6 * C57BL/6J * SJL

Additional - Slc6a8^tm1.2Clar related