JAX Mouse Strain Datasheet - 008333

B6;129P2-Dld^tm1Ptl/J

Stock No:: 008333

Targeted Mutation

Cryo Recovery

Overview

These Dld (dihydrolipoamide dehydrogenase or E3 component) mutant mice may be useful to study early murine embryonic metabolism, including glucose and mitochondrial metabolism during the early postimplantation period. As altered energy metabolism and reductions in alpha-ketoacid dehydrogenase complexes have also been associated with many neurodegenerative disorders, these mice may also be useful in studies related to Parkinson's disease, Huntington's disease, and/or Alzheimer's disease. Because the metabolic disturbances associated with E3 deficiency (Dld deficiency) cause a variant of Maple Syrup Urine Disease (MSUD) in which there is an accompanying lactic acidosis due to concomitant deficiency of pyruvate dehydrogenase complex, these mice may be useful in such studies or in conjunction with iMSUD mice (Stock No. 006999).

Donating Investigator

Mulchand S Patel, SUNY at Buffalo

Genetic overview

Genetic Background	Generation

Dld^tm1Ptl

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Dld	dihydrolipoamide dehydrogenase

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Research Applications

Developmental Biology Research
Metabolism Research
Neurobiology Research
Research Tools

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Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed Description

Mice heterozygous for the Dld (dihydrolipoamide dehydrogenase or E3 component) targeted mutation are viable and fertile. Heterozygous mice exhibit approximately half of wild-type enzymatic activity levels for E3 and all affected mitochondrial multienzyme complexes. Heterozygotes (on a C57BL/6;129P2 genetic background) exhibit increased vulnerability to treatments with MPTP (dopaminergic neurotoxin used to induce Parkinson's disease-like lesions), malonate (inhibitor of cellular respiration used to mimic Huntington's disease features), and 3-NP (mitochondrial toxin used to mimic Huntington's disease features). Homozygous mice exhibit normal development and metabolism during the preimplantation period, explained by the persistence of E3 enzyme from the oocyte. Homozygotes exhibit developmental delays shortly after implantation (7.5 to 8.5 days postcoitum (dpc)) and cease development within the subsequent two days. These Dld mutant mice may be useful to study early murine embryonic metabolism, including glucose and mitochondrial metabolism during the early postimplantation period. As altered energy metabolism and reductions in alpha-ketoacid dehydrogenase complexes have also been associated with many neurodegenerative disorders, these mice may also be useful for studying Parkinson's disease, Huntington's disease, and/or Alzheimer's disease. Because the metabolic disturbances associated with E3 deficiency (Dld deficiency) cause a variant of Maple Syrup Urine Disease (MSUD) in which there is an accompanying lactic acidosis due to concomitant deficiency of pyruvate dehydrogenase complex, these mice may be useful in such studies or in conjunction with iMSUD mice (Stock No. 006999).

Development

A targeting vector was designed to insert a beta actin promoter-driven neomycinphosphotransferase gene (lacking a polyA signal) into exon 10 of the targeted gene. The construct was electroporated into 129P2/OlaHsd-derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and chimeric males were bred with C57BL/6 females to produce heterozygous mutant mice. These heterozygotes were subjected to an additional round of breeding with C57BL/6J inbred mice, and then maintained by interbreeding of heterozygous animals for many generations prior to arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred to C57BL/6J for at least one generation to establish the colony.

Control Suggestions

Wild-type from the colony

Approximate Controls

100492 B6129PF1/J

Additional Information

Considerations for Choosing Controls

Selected References

Johnson MT; Yang HS; Magnuson T; Patel MS. 1997. Targeted disruption of the murine dihydrolipoamide dehydrogenase gene (Dld) results in perigastrulation lethality. Proc Natl Acad Sci U S A 94(26):14512-7. PubMed: 9405644 MGI: J:45074
Klivenyi P; Starkov AA; Calingasan NY; Gardian G; Browne SE; Yang L; Bubber P; Gibson GE; Patel MS; Beal MF. 2004. Mice deficient in dihydrolipoamide dehydrogenase show increased vulnerability to MPTP, malonate and 3-nitropropionic acid neurotoxicity. J Neurochem 88(6):1352-60. PubMed: 15009635 MGI: J:107994
Starkov AA; Fiskum G; Chinopoulos C; Lorenzo BJ; Browne SE; Patel MS; Beal MF. 2004. Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen species. J Neurosci 24(36):7779-88. PubMed: 15356189 MGI: J:133657

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Genetics

Dld^tm1Ptl

Allele Symbol: Dld^tm1Ptl

Allele Name	targeted mutation 1, Mulchand S Patel
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Dld^-; Dld^tm1mjp
Gene Symbol and Name	Dld, dihydrolipoamide dehydrogenase
Gene Synonym(s)	AI315664; AI746344; DLDD; DLDH; E3; GCSL; LAD; PHE3; branched chain alpha-keto acid dehydrogenase complex subunit E3; dihydrolipoyl dehydrogenase; expressed sequence AI315664; expressed sequence AI746344
Strain of Origin	129P2/OlaHsd
Chromosome	12
Molecular Note	Exon 10 was disrupted by the insertion of a neomycin selection cassette. Northern blot analysis of total hepatic and renal RNA showed that transcript levels are reduced by approximately 50% in heterozygous mice. RT-PCR analysis confirmed that the neo transgene was not excised via an altered splicing pattern.
Mutations Made By	Mark Johnson, Case Western Reserve University

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Developmental Biology Research
- Embryonic Lethality (Homozygous)
Metabolism Research
- Enzyme Deficiency
- Free Radical Research
Neurobiology Research
- Alzheimer's Disease
- Huntington's disease
- Metabolic Defects
- Neurodegeneration
- Parkinson's Disease
  - increased vulnerability to MPTP
Research Tools
- Developmental Biology Research
- Metabolism Research
- Neurobiology Research

Mammalian Phenotype Terms by Genotype

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

Genotype: Dld^tm1Ptl/Dld^tm1Ptl
involves: 129P2/OlaHsd * Black Swiss

mortality/aging

embryonic lethality between implantation and somite formation, complete penetrance
- homozygous null embryos exhibit peri-gastrulation lethality and are resorbed by 9.5 dpc

embryo phenotype

abnormal visceral endoderm morphology
- at 7.5 dpc, the mutant visceral endoderm appears to proliferate relatively longer and forms a thickened columnar layer instead of the unicellular flat squamous layer found in wild-type

decreased embryo size
- at 7.5 dpc, mutant embryos are noticeably smaller than wild-type embryos

embryonic growth arrest
- homozygous null embryos display a developmental cessation at the onset of gastrulation
- no mutant embryos develop normally to 8.5 dpc

embryonic growth retardation
- at 7.5 dpc, mutant embryos resemble 6.5-dpc wild-type egg cylinders in size and proportion
- homozygous null embryos display a developmental delay at 7.5 dpc

growth/size/body region phenotype

decreased embryo size
- at 7.5 dpc, mutant embryos are noticeably smaller than wild-type embryos

embryonic growth retardation
- at 7.5 dpc, mutant embryos resemble 6.5-dpc wild-type egg cylinders in size and proportion
- homozygous null embryos display a developmental delay at 7.5 dpc

References

Johnson MT; Yang HS; Magnuson T; Patel MS. 1997. Targeted disruption of the murine dihydrolipoamide dehydrogenase gene (Dld) results in perigastrulation lethality. Proc Natl Acad Sci U S A 94(26):14512-7. PubMed: 9405644 MGI: J:45074
Klivenyi P; Starkov AA; Calingasan NY; Gardian G; Browne SE; Yang L; Bubber P; Gibson GE; Patel MS; Beal MF. 2004. Mice deficient in dihydrolipoamide dehydrogenase show increased vulnerability to MPTP, malonate and 3-nitropropionic acid neurotoxicity. J Neurochem 88(6):1352-60. PubMed: 15009635 MGI: J:107994
Starkov AA; Fiskum G; Chinopoulos C; Lorenzo BJ; Browne SE; Patel MS; Beal MF. 2004. Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen species. J Neurosci 24(36):7779-88. PubMed: 15356189 MGI: J:133657

Additional - Dld^tm1Ptl related

Calingasan NY; Ho DJ; Wille EJ; Campagna MV; Ruan J; Dumont M; Yang L; Shi Q; Gibson GE; Beal MF. 2008. Influence of mitochondrial enzyme deficiency on adult neurogenesis in mouse models of neurodegenerative diseases. Neuroscience 153(4):986-96. PubMed: 18423880 MGI: J:139376
Johnson M; Vang P; Filipovits J; Gardner D. 2009. Maternal enzyme masks the phenotype of mouse embryos lacking dihydrolipoamide dehydrogenase. Reprod Biomed Online 19(1):79-88. PubMed: 19573295 MGI: J:162183
Kiss G; Konrad C; Doczi J; Starkov AA; Kawamata H; Manfredi G; Zhang SF; Gibson GE; Beal MF; Adam-Vizi V; Chinopoulos C. 2013. The negative impact of alpha-ketoglutarate dehydrogenase complex deficiency on matrix substrate-level phosphorylation. FASEB J 27(6):2392-406. PubMed: 23475850 MGI: J:199956

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Please inquire about possible genotypes.

Progeny testing is not required

The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks.

The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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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Licensing Information

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Dldtm1Ptl

Allele Symbol: Dldtm1Ptl

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Dldtm1Ptl/Dldtm1Ptlinvolves: 129P2/OlaHsd * Black Swiss

mortality/aging

embryo phenotype

growth/size/body region phenotype

References

Additional - Dldtm1Ptl related

Genotyping Protocols

Breeding Considerations

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Progeny testing is not required

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

Dld^tm1Ptl

Allele Symbol: Dld^tm1Ptl

Genotype: Dld^tm1Ptl/Dld^tm1Ptl
involves: 129P2/OlaHsd * Black Swiss

Additional - Dld^tm1Ptl related