Overview

These Ucn (urocortin) knockout mice exhibit an altered corticosterone response to repeated restraint stress and cold exposure and may be useful in studies of addiction and long-term neuroadaptations.

Donating Investigator

Abdul Abou-Samra, Wayne State University School of Medicine

Genetic overview

Genetic Background	Generation

Ucn^tm1Abas

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ucn	urocortin

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Research Applications

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Urocortin is a corticotropin-releasing hormone family member and a stress-related neuropeptide involved in the hypothalamo-pituitary-adrenal axis and has been implicated in processes that link stress responses with addiction and long-term neuroadaptations. These mice carry a knockout allele of the Ucn (urocortin) gene. Homozygotes have elevated basal corticosterone levels. Male homozygotes do not adapt to repeated restraint stress, exhibiting increased corticosterone response when compared to wildtype controls. Female homozygotes display partial adaptation to repeated restraint stress. Homozygotes do not respond to 2 hours of cold exposure with elevated corticosterone levels. When cold exposure follows restraint stress, female homozygotes exhibit a significantly higher increase in circulating corticosterone levels when compared to wildtype controls, while male homozygotes exhibit no corticosterone response. Mice that are homozygous for the mutation are viable and fertile. No gene product (mRNA or protein) is detected by RT-PCR of total brain RNA or in situ hybridization analysis of Edinger-Westphal nucleus tissue from brain. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background.

Development

A targeting vector containing a NEO cassette was used to disrupt coding sequence after the initiation codon. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The donating investigator reports that the resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for 6 generations (see SNP note below). Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Zalutskaya AA; Arai M; Bounoutas GS; Abou-Samra AB. 2007. Impaired adaptation to repeated restraint and decreased response to cold in urocortin 1 knockout mice. Am J Physiol Endocrinol Metab 293(1):E259-63PubMed: 17456638 MGI: J:122730

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Genetics

Ucn^tm1Abas

Allele Symbol: Ucn^tm1Abas

Allele Name	targeted mutation 1, Abdul Abou-Samra
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Ucn^tm1Aaz; Ucn1-KO
Gene Symbol and Name	Ucn, urocortin
Gene Synonym(s)
Strain of Origin	129S4/SvJae
Chromosome	5
Molecular Note	A targeting vector was designed to replace the coding sequence after the initiator methionine with a neomycin resistance cassette. In situ hybridization was used to confirm absence of protein expression.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Ucn^tm1Abas/Ucn^tm1Abas
B6.129S4-Ucn

behavior/neurological phenotype

abnormal emotion/affect behavior
- male mutant mice do not show adaptation to stress with repeated restraint, in contrast to wild-type controls
- neither male or female mutant mice show a corticosterone response to 2-hour cold exposure

homeostasis/metabolism phenotype

abnormal circulating corticosterone level
- male and female mutant mice have similar basal corticosterone levels, whereas wild-type males show higher levels than females
- males show no corticosterone response to cold exposure when they are subjected to repeated restraint, in contrast to response to restraint alone; female mutants show significant corticosterone response after repeated restraint
- neither male or female mutant mice show a corticosterone response to 2-hour cold exposure
- unlike wild-type animals, males and females do not show any corticosterone response to cold exposure

increased circulating corticosterone level
- levels after 15 minutes of restraint rise to 274 ng/ml in mutants vs 215 ng/ml in wild-type; with repeated restraint, levels in wild-type fall to 142 ng/ml, but continue to increase in mutant mice to 480 ng/ml
- basal level in blood of males is higher (188.1 ng/ml) than in wild-type controls (65.6 ng/ml)

References

Zalutskaya AA; Arai M; Bounoutas GS; Abou-Samra AB. 2007. Impaired adaptation to repeated restraint and decreased response to cold in urocortin 1 knockout mice. Am J Physiol Endocrinol Metab 293(1):E259-63PubMed: 17456638 MGI: J:122730

Additional - Ucn^tm1Abas related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Ucnalternate2
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129S4-Ucn^tm1Abas/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #020103 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
	Heterozygous or Wildtype for Ucn<tm1Abas>

Related Products and Services

Frozen Mouse Embryo	B6.129S4-Ucn<tm1Abas>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S4-Ucn<tm1Abas>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S4-Ucn<tm1Abas>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129S4-Ucn<tm1Abas>/J Frozen Embryo	$3373.50

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Ucntm1Abas

Allele Symbol: Ucntm1Abas

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Ucntm1Abas/Ucntm1AbasB6.129S4-Ucn

behavior/neurological phenotype

homeostasis/metabolism phenotype

References

Additional - Ucntm1Abas 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

Licensing Information

Ucn^tm1Abas

Allele Symbol: Ucn^tm1Abas

Genotype: Ucn^tm1Abas/Ucn^tm1Abas
B6.129S4-Ucn

Additional - Ucn^tm1Abas related