Strain Detail Sheet

Strain Name    :

B6.129S6-Acadltm1Uab

Stock Number :

000352-MU

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Acadltm1Uab
Name: targeted mutation 1, University of Alabama
Alteration at locus: Knockout
Gene Symbol: Acadl
Name: acyl-Coenzyme A dehydrogenase, long-chain
Chromosome: 1
Alteration at locus: Knockout

Genetic Alterations:
Induced duplication of exons 3 & 4, with a neo cassette in intron 4.

Genotype Determination:

ES Cell Line: TC1/TC-1 derived from B6;129S6

Strain Description [Including phenotype, strain background, strain development and suggested control mice]

Phenotype

Homozygous: Fasting induced hypoketotic-hypoglycemia, fatty liver and heart, cold intolerance, gestational loss, organic aciduria, cardiac hypertrophy, sudden death

Hemizygous: gestational loss


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype

The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
Acadltm1Uab/Acadl+
        involves: 129S6/SvEvTac * C57BL/6NTac
  • mortality/aging
    • partial prenatal lethality (MGI Ref ID J:51660)
      • incomplete penetrance
  • reproductive system phenotype
    • decreased litter size (MGI Ref ID J:51660)
      • fewer than expected number of pups
Acadltm1Uab/Acadltm1Uab
        involves: 129S6/SvEvTac * C57BL/6NTac
  • mortality/aging
    • partial prenatal lethality (MGI Ref ID J:51660)
      • partial embryonic lethality, lower than expected number of pups
    • premature death (MGI Ref ID J:51660)
      • a small number of animals die suddenly between 2-14 weeks of age
  • cardiovascular system phenotype
    • abnormal heart morphology (MGI Ref ID J:51660)
      • after an overnight fast, mutants develop microvesicular cardiac lipidosis (cardiac lesions)
      • cardiac fibrosis (MGI Ref ID J:51660)
        • 10% of adult males have severe, multifocal myocardial fibrosis
    • abnormal heart morphology (MGI Ref ID J:72193)
      • fasted mice display fatty change in hearts
      • cardiac fibrosis (MGI Ref ID J:51660)
        • 10% of adult males have severe, multifocal myocardial fibrosis
  • homeostasis/metabolism phenotype
    • abnormal adaptive thermogenesis (MGI Ref ID J:50729)
      • mutant mice tested were very sensitive to the cold, with rectal temperature dropping 10-15 degrees C within 2 hours of exposure to 4 degrees C
    • abnormal enzyme/coenzyme activity (MGI Ref ID J:51660)
      • cultured fibroblasts show a 28% reduction in ability to dehydrogenate palmitoyl-CoA compared to wild-type
    • abnormal enzyme/coenzyme activity (MGI Ref ID J:72193)
      • reduction in mitochondrial acyl-CoA dehydrogenase activity toward octanoyl-CaA, palmitoyl-CoA, 2,6-dimethlylheptanoyl-CoA, and Oleoyl-CoA in liver, heart and skeletal muscle
    • abnormal lipid homeostasis (MGI Ref ID J:72193)
      • fasted mice display fatty change in hearts
      • increased circulating free fatty acid level (MGI Ref ID J:51660)
        • fasted mutants show an elevation in serum FFA levels
      • increased fatty acid level (MGI Ref ID J:72193)
        • serum fatty acids C14:2 and C14:1 are elevated
        • significant accumulation of liver fatty acids, with the highest absolute elevation of Myristate (C14) and the largest proportionate increase of C14:1 with respect to wild-type levels
        • increased unsaturated fatty acid level (MGI Ref ID J:51660)
          • specific elevations in unsaturated fatty acids: docenedioic, tetradecenedioic, tetradecadienoic, oleic and linoleic acids
      • lipidosis (MGI Ref ID J:51660)
        • lipid accumulation in the heart
    • aciduria (MGI Ref ID J:72193)
      • significantly elevated suberic acid (C8:0) and octenedioic acid (C8:1) in the urine of fasted, but not fed, mice compared to wild-type
    • aciduria (MGI Ref ID J:51660)
      • urine organic analysis of fasted mice shows excretion of high levels of adipic, octenedioic, decenedioic, and hydroxydecenedioic acids compared to wild-type, indicating dicarboxylic aciduria
    • hypoglycemia (MGI Ref ID J:51660)
      • fasted mutants have reduced mean serum glucose concentration, however concentrations are highly varied
    • increased circulating carnitine level (MGI Ref ID J:72193)
      • C10, C12 and C14 acylcarnitine esters are elevated
      • concentration of total acylcarnitine metabolites is higher than in homozygous Acadvltm1Uab mutants or in wild-type mice
      • C14:2 and C14:1 acylcarnitine esters are elevated in the blood
  • liver/biliary system phenotype
    • abnormal bile composition (MGI Ref ID J:51660)
      • bile of fasted mutants contains extremely high concentrations of C14:1 and C14:2 acylcarnitines
    • hepatic steatosis (MGI Ref IDs J:51660, J:72193)
      • after an overnight fast, mutants develop severe and diffuse micro- and macrovesicular hepatic steatosis (MGI Ref ID J:51660)
      • fasted mice display severe hepatosteatosis with predominantly large, uniformly distributed droplets throughout the livers (MGI Ref ID J:72193)
  • reproductive system phenotype
    • decreased litter size (MGI Ref ID J:51660)
    • decreased litter size (MGI Ref ID J:72193)
      • on average 6.7 pups per litter compared to 8.5 in wild-type
  • renal/urinary system phenotype
    • aciduria (MGI Ref ID J:51660)
      • urine organic analysis of fasted mice shows excretion of high levels of adipic, octenedioic, decenedioic, and hydroxydecenedioic acids compared to wild-type, indicating dicarboxylic aciduria
    • aciduria (MGI Ref ID J:72193)
      • significantly elevated suberic acid (C8:0) and octenedioic acid (C8:1) in the urine of fasted, but not fed, mice compared to wild-type

Strain of Origin: 129S6/SvEvTac

Strain genetic background: C57BL/6NTac

Suggested Control Mice: Wild-type littermates

Research Applications

  • Cardiovascular
  • Diabetes/Obesity
  • Metabolism
  • Models for Human Disease
  • Reproduction

Strain Origin

Donor: Phillip Wood, D.V.M., Ph.D., University of Alabama at Birmingham.

Primary Reference:

  • Kurtz DM, Rinaldo P, Rhead WJ, Tian L, Millington DS, Vockley J, Hamm DA, Brix AE, Lindsey JR, Pinkert CA, O'Brien WE, Wood PA. Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation. Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15592-7. (Medline PMID: 9861014)
  • Guerra C, Koza RA, Walsh K, Kurtz DM, Wood PA, Kozak LP. Abnormal nonshivering thermogenesis in mice with inherited defects of fatty acid oxidation. J Clin Invest. 1998 Nov 1;102(9):1724-31. PMID: 9802886 (Medline PMID: 9802886)
  • Cox KB, Hamm DA, Millington DS, Matern D, Vockley J, Rinaldo P, Pinkert CA, Rhead WJ, Lindsey JR, Wood PA. Gestational, pathologic and biochemical differences between very long-chain acyl-CoA dehydrogenase deficiency and long-chain acyl-CoA dehydrogenase deficiency in the mouse. Hum Mol Genet. 2001 Sep 15;10(19):2069-77. PMID: 11590124 (Medline PMID: 11590124 )

Colony and Husbandry Information

Special Considerations

Must be protected from the cold.

Health Status Report

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@missouri.edu.

Appearance

Coat color: Nonagouti

Other:

Breeding

MMRRC Breeding System: Backcross

Breeding Scheme(s):

  • C57BL/6 female x Heterozygous male

Generation: N10 As of: 1/2005

Overall Breeding Performance: Excellent

Reproductive Statistics

Viability and Fertility:FemaleMale
Homozygotes are viable: Unknown Unknown
Homozygotes are fertile: Unknown Unknown
Heterozygotes are fertile: Unknown Yes

Age Reproductive Decline: Unknown Unknown

Average litter size: 5 - 8

Recommended wean age: 4 weeks

Order Request Information

Availability Level

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Conditions of Distribution [Including applicable technology transfer agreements]

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Fees

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # - Description Distribution
Fee/unit (US $)
Units Notes
000352-MU-RESUSLitter recovered from cryo-archive
$2,022.00
Non-Profit
Litter Recovered litter1; additional fees for any special requests.
000352-MU-SPERMCryo-preserved spermatozoa
$437.00
Non-Profit
Aliquot Approximate quantity.2

1 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

3 An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section above). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



The MMRRC is a collaborative effort, funded by grants from DPCPSI of the NIH.

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