Overview

Also Known As:SERT-Cre

The SERT-cre (SERT^cre) "knock-in" allele has a nuclear-localized Cre recombinase inserted just upstream of the first coding ATG of the serotonin transporter gene (Slc6a4; SERT or 5-HTT). This was designed to both abolish gene function and place Cre recombinase expression under the control of the SERT promoter/enhancer elements.

Donating Investigator

Xiaoxi Zhuang, The University of Chicago

Genetic overview

Genetic Background	Generation
	N10+pN2F1 (2019-01-31 00:00:00)

Slc6a4^tm1(cre)Xz

Allele Type	Gene Symbol	Gene Name
Targeted (Recombinase-expressing)	Slc6a4	solute carrier family 6 (neurotransmitter transporter, serotonin), member 4

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Research Applications

Research Tools
Neurobiology Research

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Base Price

Starting at:

$270.00 Domestic price for female 4-week

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Details

Detailed Description

The SERT-cre (SERT^cre) "knock-in" allele has a nuclear-localized Cre recombinase inserted just upstream of the first coding ATG of the serotonin transporter gene (Slc6a4 ; SERT or 5-HTT). This was designed to both abolish SERT gene function and place Cre recombinase expression under the control of the SERT promoter/enhancer elements.

Cre recombinase activity is directed to serotonergic neurons. In adult mice, Cre recombinase activity is predominantly observed in serotonin producing neurons of the brain (raphe nuclei) and the gut (enterochromaffin cells). During development, Cre recombinase activity is observed in thalamus, cingulate cortex and hippocampus CA3 region pyramidal cells, as well as more broadly in several non-serotonin neurons of the brain and in neural crest derivatives. While SERT expression is not expected in adult thalamus, cingulate cortex or hippocampus CA3 region pyramidal cells, Cre reporter staining observed in these adult tissues may be attributed to SERT expression patterns during late embryonic and early postnatal development.

Homozygous SERT-cre mice are viable and fertile. Failure of serotonin uptake/clearance results in behavioral, neurological, and biochemical abnormalities (donating investigator points to PMID 17356573, Sanders, 2007). Heterozygotes have no known phenotype.

Of note, breeding homozygous SERT-Cre females with Cre reporter males results in sporadic germline cre expression (presumably due mainly to SERT expression in murine ovarian cells). For experiments, the donating investigator recommends breeding heterozygous SERT-Cre males with Cre reporter females as the frequency of germline cre expression is greatly diminished.

Furthermore, Luo et al. 2020 Neuron 106:37 Table 1 shows germline recombination in offspring (F2) of Cre;floxed double mutant (F1) mice bred to floxed and/or wildtype mice. The authors also note that in general, the frequency of recombination in Cre;floxed double mutant germline cells appears to be considerably higher than in zygotes produced by breeding Cre mice to floxed mice.
This reports that both female and male SERT-Cre;floxed double mutants bred to floxed mice produced some offspring with germline deletion of the floxed allele [observed from >20 litters (up to 100% in some litters) when using Cre female or Cre male]. As such, for Cre-lox experiments and to reduce the frequency of germline deletion of the floxed allele, researchers may consider breeding SERT-Cre heterozygous mice to floxed mice.

If the recombinase activity pattern of this allele is further characterized by the Genetic Resource Science group at The Jackson Laboratory, such findings will be reported on the Mouse Genome Informatics (MGI) Allele Detail entry. This same information may also be found searching the MGI Recombinase Activity and MGI Gene Expression + Recombinase Activity Comparison Matrix.

SERT-deficient mice on a C57BL/6 congenic background are also available (see Stock No. 008355).

Development

A targeting vector was designed to insert a nuclear-localized Cre recombinase coding sequence followed by an FRT-flanked, reverse-oriented PGK-neo-pA cassette into the 5' UTR of the Slc6a4 (SERT or 5-HTT) locus. This introduction was made downstream of the endogenous promoter and immediately upstream of the SERT translational start codon. This construct was electroporated into 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺-derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts, and the resulting chimeric males were bred with 129Sv/J females to generate SERT-cre mice. The neomycin cassette was excised. This strain was subsequently backcrossed to C57BL/6J for more than 10 generations by the donating lab.

Expression Data

Expressed Gene	cre, cre recombinase, bacteriophage P1
Site of Expression	Serotonergic neurons

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Zhuang X; Masson J; Gingrich JA; Rayport S; Hen R. 2005. Targeted gene expression in dopamine and serotonin neurons of the mouse brain. J Neurosci Methods 143(1):27-32PubMed: 15763133 MGI: J:115426

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Genetics

Slc6a4^tm1(cre)Xz

Allele Symbol: Slc6a4^tm1(cre)Xz

Allele Name	targeted mutation 1, Xiaoxi Zhuang
Allele Type	Targeted (Recombinase-expressing)
Allele Synonym(s)	SERT-cre
Gene Symbol and Name	Slc6a4, solute carrier family 6 (neurotransmitter transporter, serotonin), member 4
Gene Synonym(s)
Expressed Gene	cre, cre recombinase, bacteriophage P1
Site of Expression	Serotonergic neurons
Strain of Origin	129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Chromosome	11
Molecular Note	A targeting vector was constructed by inserting a cassette with the cre recombinase coding sequence, a nuclear translocation signal, and a PGK-neo gene flanked by FRT sites, into the 5'-UTR of the Slc6a4 gene. After homologous recombination in ES cells, mice with cre recombinase expressed from the Slc6a4 locus were produced. Cre recombinase expression is detected in the Raphe nuclei. Flp-mediated recombination removed the FRT-flanked neo cassette.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

sudden infant death syndrome

Research Areas By Phenotype

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

Research Tools
- Neurobiology Research
- Cre-lox System
  - Cre Recombinase Expression
Neurobiology Research
- Cre-lox System
  - Cre Recombinase expression in neural tissue

Mammalian Phenotype Terms by Genotype

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

Genotype: Slc6a4^tm1(cre)Xz/Slc6a4⁺
involves: 129S1/Sv * C57BL/6 * SJL

normal phenotype

no abnormal phenotype detected
- Normal - mice are viable and fertile

Genotype: Slc6a4^tm1(cre)Xz/Slc6a4^tm1(cre)Xz
involves: 129S1/Sv * C57BL/6

cardiovascular system phenotype

cardiac fibrosis
- at E18.5, mice exhibit an increase in collagen accumulation in the myocardium and valvular and perivascular regions of the heart unlike wild-type mice

mortality/aging

postnatal lethality, incomplete penetrance
- 75% of mice die with the first week after birth

References

Zhuang X; Masson J; Gingrich JA; Rayport S; Hen R. 2005. Targeted gene expression in dopamine and serotonin neurons of the mouse brain. J Neurosci Methods 143(1):27-32PubMed: 15763133 MGI: J:115426

Additional References

De Leon Reyes NS; Mederos S; Varela I; Weiss LA; Perea G; Galazo MJ; Nieto M. 2019. Transient callosal projections of L4 neurons are eliminated for the acquisition of local connectivity. Nat Commun 10(1):4549PubMed: 31591398 MGI: J:281346

Additional - Slc6a4^tm1(cre)Xz related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Slc6a4 Alternate1
- Genotyping resources and troubleshooting
Dietary Information
- New Diet as of March 2015: Lab Diet® 5K0Q (6% fat)
Breeding Considerations

When maintaining a live SERT-Cre colony, homozygous mice may be bred together.

For Cre-lox experiments and to reduce the frequency of germline deletion of the floxed allele, researchers may consider breeding SERT-Cre heterozygous mice to floxed mice, perhaps heterozygous SERT-Cre males with floxed females. See Detailed Description for more details.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Homozygote
- Homozygote x Heterozygote
Citation
When using the SERT-Cre mouse strain in a publication, please cite the originating article(s) and include JAX stock #014554 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX18 (Maximum)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Slc6a4<tm1(cre)Xz>

Related Products and Services

Frozen Mouse Embryo	B6.129(Cg)-Slc6a4<tm1(cre)Xz>/J	$2595.00
Frozen Mouse Embryo	B6.129(Cg)-Slc6a4<tm1(cre)Xz>/J	$2595.00
Frozen Mouse Embryo	B6.129(Cg)-Slc6a4<tm1(cre)Xz>/J	$3373.50
Frozen Mouse Embryo	B6.129(Cg)-Slc6a4<tm1(cre)Xz>/J	$3373.50

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Also Known As:SERT-Cre

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Slc6a4tm1(cre)Xz

Allele Symbol: Slc6a4tm1(cre)Xz

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not 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: Slc6a4tm1(cre)Xz/Slc6a4+involves: 129S1/Sv * C57BL/6 * SJL

normal phenotype

Genotype: Slc6a4tm1(cre)Xz/Slc6a4tm1(cre)Xzinvolves: 129S1/Sv * C57BL/6

cardiovascular system phenotype

mortality/aging

References

Additional References

Additional - Slc6a4tm1(cre)Xz related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

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

Slc6a4^tm1(cre)Xz

Allele Symbol: Slc6a4^tm1(cre)Xz

Genotype: Slc6a4^tm1(cre)Xz/Slc6a4⁺
involves: 129S1/Sv * C57BL/6 * SJL

Genotype: Slc6a4^tm1(cre)Xz/Slc6a4^tm1(cre)Xz
involves: 129S1/Sv * C57BL/6

Additional - Slc6a4^tm1(cre)Xz related