Overview

These Pdha1^flox8 mutant mice possess loxP sites flanking exon 8 of the pyruvate dehydrogenase E1 alpha 1 (Pdha1) gene. This strain may be useful for studying lipid metabolism, glucose metabolism, and insulin sensitivity.

Donating Investigator

Mulchand S Patel, SUNY at Buffalo

Genetic overview

Genetic Background	Generation

Pdha1^tm1Ptl

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Pdha1	pyruvate dehydrogenase E1 alpha 1

View Genetics

Research Applications

Metabolism Research
Diabetes and Obesity Research
Research Tools
Internal/Organ Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

These Pdha1^flox8 mutant mice possess loxP sites flanking exon 8 of the pyruvate dehydrogenase E1 alpha 1 (Pdha1) gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. PDHA1 is catalytic component of the pyruvate dehydrogenase complex (PDC) which is a mitochondrial multienzyme complex involved in lipid synthesis, glucose homeostasis, and metabolism of carbohydrates. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 8 deleted in cre-expressing tissues. For example, when crossed to a strain expressing Cre recombinase in the liver, this mutant mouse strain may be useful for studying lipid metabolism, glucose metabolism, and insulin sensitivity in the liver.

When bred to a strain expressing Cre recombinase in the central and periphal nervous system (see Stock No. 003771 for example), this mutant mouse strain may be useful in studies of neuronal migration, axonal growth and cell-cell interactions.

When bred to a strain expressing Cre recombinase in the oocyte (see Stock No. 003651 for example), this mutant mouse strain may be useful in studies of oogenesis.

When bred to a strain expressing Cre recombinase in skeletal and cardiac muscle (see Stock No. 006475 for example), this mutant mouse strain may be useful in studies of cardiac glucose metabolism.

Development

A targeting vector was designed to insert a single loxP site upstream of exon 8, and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 8 of the pyruvate dehydrogenase E1 alpha 1 (Pdha1) gene. The construct was electroporated into 129P2/OlaHsd-derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a pMC-Cre expression plasmid to delete the neo cassette. Resulting ES cells contained multiple gene rearrangments; intact floxed-exon 8, intact floxed-neo cassette, or excision of both exon 8 and the neo cassette. Correctly targeted ES cells, containing only the floxed-exon 8, were injected into C57BL/6 blastocysts and resulting chimeric males were bred with 129 females. These mice were backcrossed to C57BL/6 mice for at least 10 generations to establish a colony of Pdha1^flox8 mice. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation.

Control Suggestions

Heterozygote from the colony
Wild-type from the colony

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Johnson MT; Mahmood S; Hyatt SL; Yang HS; Soloway PD; Hanson RW; Patel MS. 2001. Inactivation of the murine pyruvate dehydrogenase (Pdha1) gene and its effect on early embryonic development. Mol Genet Metab 74(3):293-302PubMed: 11708858 MGI: J:74192

View All References

Genetics

Pdha1^tm1Ptl

Allele Symbol: Pdha1^tm1Ptl

Allele Name	targeted mutation 1, Mulchand S Patel
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	Pdha1^flox8
Gene Symbol and Name	Pdha1, pyruvate dehydrogenase E1 alpha 1
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	X
Molecular Note	Exon 8 was left flanked by loxP sites after a downstream floxed tk-neo cassette was excised by the in vitro expression of cre recombinase. Western blot analysis of homozygous mutant ES cells showed normal levels of both isoforms produced by the endogenous allele. Mice carrying this allele were bred to transgenic mice expressing cre in the germline to generate Pdha1^tm1.1Ptl.
Mutations Made By	Mulchand Patel, SUNY at Buffalo

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Metabolism Research
- Lipid Metabolism
Diabetes and Obesity Research
- Impaired Insulin Processing
Research Tools
- Cre-lox System
  - loxP-flanked Sequences
Internal/Organ Research
- Liver 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: Pdha1^tm1Ptl/Y Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6 * FVB/N * SJL

mortality/aging

prenatal lethality, complete penetrance
- mice die prenatally

Genotype: Pdha1^tm1Ptl/Pdha1^tm1Ptl Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6 * FVB/N * SJL

mortality/aging

prenatal lethality, incomplete penetrance
- 50% fewer than expected mice are born

nervous system phenotype

abnormal brain white matter morphology
- white matter structures of the forebrain including the commissural anterior (pars anterior), lateral olfactory tract, and corpus callosum are smaller and underdeveloped

abnormal cerebellar granule layer morphology
- the granule cell layer is reduced in an irregular pattern

abnormal cerebellar molecular layer
- small with fewer fibers

abnormal cerebellar peduncle morphology
- the size of the cerebellar peduncles are smaller than in wild-type mice

abnormal cerebellum deep nucleus morphology
- the cerebellar nuclei within the white matter exhibits local heterotopias and distributed neuropil

abnormal cerebral cortex pyramidal cell morphology
- pyramidal cells are not arranged in a tight cellular layer as in wild-type mice

abnormal neocortex morphology
- neuropils appear to have fewer than expected fibers
- some mice exhibit neurons clustered in local heterotopia or as single layers with a lower neuronal density in the surrounding areas unlike in wild-type mice
- the thickness of neocortex is reduced with irregularly distributed sites of disturbed cytoarchitecture compared to in wild-type mice

abnormal olfactory tract morphology
- the lateral olfactory tract is smaller and underdeveloped

abnormal paraventricular thalamic nucleus morphology

abnormal putamen morphology
- the nucleus caudatus/putamen exhibit irregular local heterotopias and fibers are less organized and of smaller diameter than in wild-type mice

abnormal thalamus morphology
- neurons within the nuclei paraventricularis and anterodorsalis are reduced in density and number compared to in wild-type mice

decreased brain weight
- at P35

decreased corpus callosum size
- small and underdeveloped

decreased Purkinje cell number

decreased stria medullaris size
- the stria medullaris is smaller and has fewer fibers than in wild-type mice

small cerebellum

Genotype: Pdha1^tm1Ptl/Pdha1^tm1Ptl Tg(Zp3-cre)93Knw/0
involves: 129P2/OlaHsd * C57BL/6J

cellular phenotype

abnormal oocyte morphology
- fewer oocytes at found at the surrounded nucleolus stage than in wild-type oocytes
- following removal of cumulus cells, a higher proportion of oocytes are at the germinal vesicle or abnormal germinal vesicle breakdown stage compared to similarly treated wild-type oocytes
- Normal - however, oocyte size is normal
- more oocytes in the cumulus-oocyte complexes are at the germinal vesicle or abnormal germinal vesicle breakdown stage than in wild-type mice
- oocytes exhibit worsening energy status during meiotic maturation unlike wild-type oocytes
- oocytes have fewer polar bodies than in wild-type mice

abnormal polar body morphology
- oocytes have fewer polar bodies than in wild-type mice
- some oocytes exhibit chromatin and spindle abnormalities with or without formation of polar bodies

reproductive system phenotype

abnormal female meiosis
- oocytes are atypical of any developmental stage unlike wild-type oocytes that are at metaphase of meiosis I or meiosis II
- some oocytes exhibit chromatin and spindle abnormalities with or without formation of polar bodies unlike wild-type oocytes
- some oocytes exhibit chromatin that is eccentrically located with only occasional evidence of discrete chromosomes or clumps of chromatin unlike in wild-type oocytes
- some oocytes have highly condensed chromatin and absence of spindle structures unlike wild-type oocytes

abnormal meiotic spindle morphology
- some oocytes exhibit chromatin and spindle abnormalities with or without formation of polar bodies
- some oocytes have highly condensed chromatin and absence of spindle structures

abnormal oocyte morphology
- fewer oocytes at found at the surrounded nucleolus stage than in wild-type oocytes
- following removal of cumulus cells, a higher proportion of oocytes are at the germinal vesicle or abnormal germinal vesicle breakdown stage compared to similarly treated wild-type oocytes
- Normal - however, oocyte size is normal
- more oocytes in the cumulus-oocyte complexes are at the germinal vesicle or abnormal germinal vesicle breakdown stage than in wild-type mice
- oocytes exhibit worsening energy status during meiotic maturation unlike wild-type oocytes
- oocytes have fewer polar bodies than in wild-type mice

abnormal polar body morphology
- oocytes have fewer polar bodies than in wild-type mice
- some oocytes exhibit chromatin and spindle abnormalities with or without formation of polar bodies

female infertility

Genotype: Pdha1^tm1Ptl/Y Tg(Ckmm-cre)5Khn/0
involves: 129P2/OlaHsd * FVB

cardiovascular system phenotype

abnormal heart left ventricle morphology
- whether mice are fed a high fat or laboratory chow diet, the left ventricular diastolic dimension is increased compared to in wild-type mice

decreased cardiac muscle contractility
- whether fed a high fat or laboratory chow diet, mice exhibit reduced fractional shortening compared to in heterozygous female mice and wild-type mice

enlarged myocardial fiber
- compared to in heterozygous female mice and wild-type mice

heart left ventricle hypertrophy

increased heart weight

mortality/aging

premature death
- when mice are weaned onto a high fat diet, male mice die 12 days after switching from a high fat diet to rodent laboratory chow
- when weaned onto rodent laboratory chow, male mice die 7 days after weaning

muscle phenotype

decreased cardiac muscle contractility
- whether fed a high fat or laboratory chow diet, mice exhibit reduced fractional shortening compared to in heterozygous female mice and wild-type mice

enlarged myocardial fiber
- compared to in heterozygous female mice and wild-type mice

heart left ventricle hypertrophy

growth/size/body region phenotype

heart left ventricle hypertrophy

increased body weight
- at 9 weeks of age

increased heart weight

homeostasis/metabolism phenotype

increased circulating insulin level

Genotype: Pdha1^tm1Ptl/Pdha1⁺ Tg(Ckmm-cre)5Khn/0
involves: 129P2/OlaHsd * FVB

cardiovascular system phenotype

abnormal heart left ventricle morphology
- when mice are transitioned from a high fat diet to a rodent laboratory diet, the left ventricular diastolic dimension is increased compared to in wild-type mice

decreased cardiac muscle contractility
- when transitioned from a high fat diet to a rodent laboratory diet, mice exhibit reduced fractional shortening compared to in wild-type mice

enlarged myocardial fiber

increased heart weight
- Normal - however, heart weight to body weight is normal
- mice exhibit increased heart weight compared to in wild-type mice

muscle phenotype

decreased cardiac muscle contractility
- when transitioned from a high fat diet to a rodent laboratory diet, mice exhibit reduced fractional shortening compared to in wild-type mice

enlarged myocardial fiber

growth/size/body region phenotype

increased body weight
- at 9 weeks of age

increased heart weight
- Normal - however, heart weight to body weight is normal
- mice exhibit increased heart weight compared to in wild-type mice

homeostasis/metabolism phenotype

increased circulating insulin level

References

Johnson MT; Mahmood S; Hyatt SL; Yang HS; Soloway PD; Hanson RW; Patel MS. 2001. Inactivation of the murine pyruvate dehydrogenase (Pdha1) gene and its effect on early embryonic development. Mol Genet Metab 74(3):293-302PubMed: 11708858 MGI: J:74192

Additional References

Gopal K; Almutairi M; Al Batran R; Eaton F; Gandhi M; Ussher JR. 2018. Cardiac-Specific Deletion of Pyruvate Dehydrogenase Impairs Glucose Oxidation Rates and Induces Diastolic Dysfunction. Front Cardiovasc Med 5:17PubMed: 29560354 MGI: J:288937

Additional - Pdha1^tm1Ptl related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Pdha1 alternative 1
- 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 B6.129P2-Pdha1^tm1Ptl/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017443 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 Pdha1<tm1Ptl>

Related Products and Services

Frozen Mouse Embryo	B6.129P2-Pdha1<tm1Ptl>/J	$2595.00
Frozen Mouse Embryo	B6.129P2-Pdha1<tm1Ptl>/J	$2595.00
Frozen Mouse Embryo	B6.129P2-Pdha1<tm1Ptl>/J	$3373.50
Frozen Mouse Embryo	B6.129P2-Pdha1<tm1Ptl>/J	$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

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Pdha1tm1Ptl

Allele Symbol: Pdha1tm1Ptl

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Pdha1tm1Ptl/Y Tg(Nes-cre)1Kln/0involves: 129P2/OlaHsd * C57BL/6 * FVB/N * SJL

mortality/aging

Genotype: Pdha1tm1Ptl/Pdha1tm1Ptl Tg(Nes-cre)1Kln/0involves: 129P2/OlaHsd * C57BL/6 * FVB/N * SJL

mortality/aging

nervous system phenotype

Genotype: Pdha1tm1Ptl/Pdha1tm1Ptl Tg(Zp3-cre)93Knw/0involves: 129P2/OlaHsd * C57BL/6J

cellular phenotype

reproductive system phenotype

Genotype: Pdha1tm1Ptl/Y Tg(Ckmm-cre)5Khn/0involves: 129P2/OlaHsd * FVB

cardiovascular system phenotype

mortality/aging

muscle phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

Genotype: Pdha1tm1Ptl/Pdha1+ Tg(Ckmm-cre)5Khn/0involves: 129P2/OlaHsd * FVB

cardiovascular system phenotype

muscle phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

References

Additional References

Additional - Pdha1tm1Ptl 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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Pdha1^tm1Ptl

Allele Symbol: Pdha1^tm1Ptl

Genotype: Pdha1^tm1Ptl/Y Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6 * FVB/N * SJL

Genotype: Pdha1^tm1Ptl/Pdha1^tm1Ptl Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6 * FVB/N * SJL

Genotype: Pdha1^tm1Ptl/Pdha1^tm1Ptl Tg(Zp3-cre)93Knw/0
involves: 129P2/OlaHsd * C57BL/6J

Genotype: Pdha1^tm1Ptl/Y Tg(Ckmm-cre)5Khn/0
involves: 129P2/OlaHsd * FVB

Genotype: Pdha1^tm1Ptl/Pdha1⁺ Tg(Ckmm-cre)5Khn/0
involves: 129P2/OlaHsd * FVB

Additional - Pdha1^tm1Ptl related