Overview

These mice harbor a targeted "null" mutation of the organic solute transporter alpha (Osta) locus and may be useful in studying cholesterol metabolism, intestinal drug absorption, intestinal bile acid absorption, bile acid synthesis, and cholesterol and bile acid homeostasis.

Donating Investigator

Paul A. Dawson, Wake Forest University Sch of Medicine

Genetic overview

Genetic Background	Generation

Slc51a^tm1Pda

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Slc51a	solute carrier family 51, alpha subunit

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Research Applications

Metabolism Research
Developmental Biology Research
Research Tools
Internal/Organ Research
Endocrine Deficiency Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Homozygous (Slc51a^-/-) mice are viable and fertile, with no mRNA or protein expression from the targeted allele. Homozygotes exhibit a small growth deficit that is ameliorated after weaning, partial impairment of intestinal bile acid absorption (impaired basolateral transport of bile acids out of the ileal epithelial cell), altered regulation of bile acid synthesis, a significantly reduced bile acid pool, intestinal lengthening and intestinal hypertrophy. Homozygous mice also have reduced hepatic Cyp7a1 expression that is inversely correlated with ileal expression of fibroblast growth factor 15 (FGF15). These mutant mice may be useful in studying cholesterol metabolism, intestinal drug absorption, intestinal bile acid absorption, bile acid synthesis, and cholesterol and bile acid homeostasis.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. Although the donating investigator reports no observed phenotypic differences between Osta-mutant mice on a C57BL/6-congenic or B6;129S6 mixed genetic background, it should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector was designed to replace exons 1 and 2 of the targeted gene with a reverse-oriented neomycin resistance cassette. The construct was electroporated into 129S6/SvEvTac-derived SM1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. Male chimera's were bred with C57BL/6J females to establish the mutant colony. Mutant mice were subsequently backcrossed to C57BL/6J for at least 8 generations prior to arrival at The Jackson Laboratory. Upon arrival, these mutant mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony. During the backcross, the Y chromosome may not have been fixed to the C57BL/6J genetic background.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Rao A; Haywood J; Craddock AL; Belinsky MG; Kruh GD; Dawson PA. 2008. The organic solute transporter alpha-beta, Ostalpha-Ostbeta, is essential for intestinal bile acid transport and homeostasis. Proc Natl Acad Sci U S A 105(10):3891-6PubMed: 18292224 MGI: J:132778

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Genetics

Slc51a^tm1Pda

Allele Symbol: Slc51a^tm1Pda

Allele Name	targeted mutation 1, Paul A Dawson
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Slc51a, solute carrier family 51, alpha subunit
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	16
Molecular Note	Exon 1 and 2 were replaced with a neo cassette. The absence of protein product was confirmed by western blot analysis on ileal extracts.
Mutations Made By	Paul Dawson, Wake Forest University Sch of Medicine

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Metabolism Research
- Lipid Metabolism
Developmental Biology Research
- Growth Defects
Research Tools
- Metabolism Research
Internal/Organ Research
- Gastrointestinal Defects
- Liver Defects
Endocrine Deficiency Research
- Gastrointestinal 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: Slc51a^tm1Pda/Slc51a^tm1Pda
involves: 129S6/SvEvTac * C57BL/6J

digestive/alimentary phenotype

abnormal feces composition
- fecal cholesterol excretion is elevated about 4-fold in both males and females

abnormal small intestine morphology
- 3 month old adult males exhibit longer small intestines than wild-type
- small intestinal hypertrophy

growth/size/body region phenotype

postnatal growth retardation
- pups exhibit a small growth deficit

homeostasis/metabolism phenotype

abnormal bile salt homeostasis
- efflux of taurocholate from tissue to the serosal side (amount of TC in serosal fluid/TC associated with tissue) is decreased
- in everted gut sac experiments, the transileal taurocholate (TC) transport is reduced by about 95% and 80% in male and female mutants, respectively, indicating impaired intestinal bile acid transport
- mutants fed exogenous bile acids (0.2% cholic acid diet) exhibit a 5-fold elevation in the rate of fecal bile acid excretion by day 2 compared to wild-type and remains constant and higher
- the bile acid FTR (daily fecal bile acid excretion/pool size) is elevated 5-fold in males and 3-fold in females

abnormal bile salt level
- bile acid pool is decreased by 70% and 65% in males and females, respectively

abnormal cholesterol level
- fecal cholesterol excretion is elevated about 4-fold in both males and females

decreased circulating cholesterol level
- 3 month old females exhibit lower plasma cholesterol levels

decreased circulating triglyceride level
- 3 month old females exhibit lower triglyceride levels

References

Rao A; Haywood J; Craddock AL; Belinsky MG; Kruh GD; Dawson PA. 2008. The organic solute transporter alpha-beta, Ostalpha-Ostbeta, is essential for intestinal bile acid transport and homeostasis. Proc Natl Acad Sci U S A 105(10):3891-6PubMed: 18292224 MGI: J:132778

Additional - Slc51a^tm1Pda related

Technical Support

CONTACT TECHNICAL SUPPORT

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

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129S6-Slc51a^tm1Pda/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #009082 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 for Osta<tm1Pda>

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

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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

Slc51atm1Pda

Allele Symbol: Slc51atm1Pda

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Slc51atm1Pda/Slc51atm1Pdainvolves: 129S6/SvEvTac * C57BL/6J

digestive/alimentary phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

References

Additional - Slc51atm1Pda 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

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

Slc51a^tm1Pda

Allele Symbol: Slc51a^tm1Pda

Genotype: Slc51a^tm1Pda/Slc51a^tm1Pda
involves: 129S6/SvEvTac * C57BL/6J

Additional - Slc51a^tm1Pda related