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| 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). | |||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N12F7pN1
Generation DefinitionsDonating Investigator Mulchand S Patel, SUNY at Buffalo 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 neomycin phosphotransferase 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 Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 100492 B6129PF1/J | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Alzheimer's Disease Models
View Alzheimer's Disease Models (107 strains)
007708 B6.129-Gt(ROSA)26Sortm1(HD*103Q)Xwy/J 003454 B6.129-Htttm3Mem/J 003597 B6.129-Htttm4Mem/J 003598 B6.129-Htttm5Mem/J 016094 B6.129P2-Git2Gt(XG510)Byg/WeisJ 016522 B6.129P2-Htttm2Detl/100J 004595 B6.129P2-Htttm2Detl/150J 016521 B6.129P2-Htttm2Detl/50J 002688 B6.129S4-Htttm1Mem/J 006471 B6.Cg-Tg(HDexon1)61Gpb/J 004360 B6;SJL-Tg(HD)63Aron/J 003627 B6C3-Tg(HD82Gln)81Dbo/J 002809 B6CBA-Tg(HDexon1)61Gpb/1J 002810 B6CBA-Tg(HDexon1)62Gpb/1J 006494 B6CBA-Tg(HDexon1)62Gpb/3J 016095 C.129P2(B6)-Git2Gt(XG510)Byg/WeisJ 008833 C57BL/6-Tg(Camk2a-UBB)3413-1Fwvl/J 007578 CBy.Cg-Tg(HDexon1)61Gpb/J 013732 FVB-Tg(NPEPPS)1Skar/J 004938 FVB-Tg(YAC128)53Hay/J 012630 FVB/N-Tg(GFAP-HTT*160Q)31Xjl/J 008197 FVB/N-Tg(HTT*97Q)IXwy/J 007247 FVB/N-Tg(YAC353G6)W7Hay/J 003640 FVB/NJ-Tg(YAC72)2511Hay/J 007749 STOCK Hap1tm1Xjl/J 003453 STOCK Htttm2Mem/J 003455 STOCK Htttm4Mem/J 003456 STOCK Htttm5Mem/J
Additional Web Information
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
Visit the Huntington's Diease Resource site for helpful information on Huntington's Disease and research resources.
Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.
Phenotype
Phenotype Information
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Leigh Syndrome; LS (DLD)
Maple Syrup Urine Disease; MSUD (DLD)
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Dldtm1Ptl/Dldtm1Ptl
involves: 129P2/OlaHsd * Black Swiss
- mortality/aging
- complete embryonic lethality between implantation and somite formation
- homozygous null embryos exhibit peri-gastrulation lethality and are resorbed by 9.5 dpc (MGI Ref ID J:45074)
- embryogenesis 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 (MGI Ref ID J:45074)
- decreased embryo size
- at 7.5 dpc, mutant embryos are noticeably smaller than wild-type embryos (MGI Ref ID J:45074)
- embryonic growth arrest
- embryonic growth retardation
- growth/size phenotype
- decreased embryo size
- at 7.5 dpc, mutant embryos are noticeably smaller than wild-type embryos (MGI Ref ID J:45074)
- embryonic growth retardation
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
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Dldtm1Ptl | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Mulchand S Patel | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Dld-; Dldtm1mjp; | ||
| Mutation Made By | Mark Johnson, Case Western Reserve University | ||
| Strain of Origin | 129P2/OlaHsd | ||
| ES Cell Line Name | E14.1 | ||
| ES Cell Line Strain | 129P2/OlaHsd | ||
| Gene Symbol and Name | Dld, dihydrolipoamide dehydrogenase | ||
| Chromosome | 12 | ||
| Gene Common Name(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; | ||
| 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. [MGI Ref ID J:45074] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Dldtm1Ptl, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
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 Ref ID 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 Ref ID 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 Ref ID J:133657]
Additional References
Dldtm1Ptl relatedCalingasan 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 Ref ID 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 Ref ID J:162183]
Health & husbandry
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Breeding & Husbandry When maintaining a live colony, heterozygous mice may be bred. Homozygous mice die in utero.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2085.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
Cryorecovery - Standard.
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 11 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. IMPORTANT NOTE: 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2710.50 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
Cryorecovery - Standard.
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 11 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. IMPORTANT NOTE: 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 100492 B6129PF1/J | (approximate) | |
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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.Ordering Information
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