Strain Name:

B6.129S5-Dhcr24tm1Lex/SbpaJ

Stock Number:

012564

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Availability:

Cryopreserved - Ready for recovery

These mice harbor a Dhcr24-knockout allele that disrupts catalysis of the last step of cholesterol biosynthesis (the conversion of desmosterol to cholesterol), and may be useful in studying cholesterol biosynthesis, epidermal development, keratinocyte differentiation, and epidermal barrier function, as well as Alzheimer's disease and tumor biology. In addition, the Dhcr24 gene (also called selective Alzheimer's disease indicator-1 (Seladin-1)) is reported to be a liver X receptor (LXR) target gene.

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

Former Names B6.129S5-Dhcr24tm1Fein/SbpaJ    (Changed: 17-AUG-12 )
Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
GenerationN14pN1
Generation Definitions
 
Donating Investigator Shailendra B Patel,   Medical College of Wisconsin

Description
Homozygous mice on the C57BL/6 genetic background die within the first postnatal day with features of lethal restrictive dermopathy; including taut, wrinkle-free, shiny skin, severe defects in epidermal maturation/epidermal barrier function (impaired epidermal development), and increased presence of hyperproliferative immature keratinocytes (defective keratinocyte differentiation). The increased transepidermal water loss/increased epidermal water content is associated with increased aquaporin-3 (AQP3) expression throughout the epidermis. Mice heterozygous for this allele are viable and fertile, with no overt phenotype. As the Dhcr24 protein functions to catalyze the last step of cholesterol biosynthesis (the conversion of desmosterol to cholesterol), homozygous disruption of this locus results in desmosterolosis: almost no cholesterol in plasma and tissues with ~99% of total sterols in the form of desmosterol. lacZ expression from the mutant allele is not characterized.

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. It should be noted that the phenotype of Dhcr24-mutant mice was originally described on a mixed C57BL/6;129S5 genetic background. We will modify the strain description if necessary as published results become available.

Development
The Dhcr24 knockout mutation was created by the laboratory of Dr. Elena Feinstein (Quark Biotech). A targeting vector was designed to delete a 249 bp region containing exon 1 of the targeted gene and replace it with a lacZ/neo selection cassette. The construct was electroporated into 129S5/SvEvBrd-derived Lex-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with albino C57BL/6 females to establish the colony. In ~2004, heterozygous mutant mice (B6;129S5 mixed background) were sent to Dr. Shailendra B. Patel (while at Medical University of South Carolina) where they were backcrossed to C57BL/6J mice for three generations. Dr. Patel moved his colony to Medical College of Wisconsin, and then further bakcrossed the colony to C57BL/6J mice for 11 more generations. Heterozygous mice backcrossed to C57BL/6J for a total of at least 14 generations were sent to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

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View Alzheimer's Disease Models     (109 strains)

Additional Web Information

Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Desmosterolosis   (DHCR24)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Dhcr24tm1Lex/Dhcr24tm1Lex

        involves: 129S5/SvEvBrd * C57BL/6
  • mortality/aging
  • partial prenatal lethality
    • the number of mice born was less than expected by Mendelian ratios   (MGI Ref ID J:87402)
  • adipose tissue phenotype
  • abnormal mesenteric fat pad morphology
    • decreased stores of mesenteric fat   (MGI Ref ID J:87402)
  • decreased subcutaneous adipose tissue amount   (MGI Ref ID J:87402)
  • growth/size/body phenotype
  • decreased body size
    • approximately 25% smaller than wild-type   (MGI Ref ID J:87402)
    • decreased body weight
      • whereas female mice reached normal weight by 4 to 5 weeks of age, male mice did not   (MGI Ref ID J:87402)
  • postnatal growth retardation   (MGI Ref ID J:87402)
  • homeostasis/metabolism phenotype
  • abnormal circulating cholesterol level
    • desmosterols accounted for approximately 99% of sterols   (MGI Ref ID J:87402)
    • tissue levels of cholesterol were nearly completely ablated   (MGI Ref ID J:87402)
    • decreased circulating cholesterol level
      • plasma contained nearly no cholesterol   (MGI Ref ID J:87402)
  • reproductive system phenotype
  • female infertility   (MGI Ref ID J:87402)
  • male infertility   (MGI Ref ID J:87402)
  • testicular atrophy
    • testes degeneration   (MGI Ref ID J:87402)
  • integument phenotype
  • decreased subcutaneous adipose tissue amount   (MGI Ref ID J:87402)
  • endocrine/exocrine gland phenotype
  • testicular atrophy
    • testes degeneration   (MGI Ref ID J:87402)
View Research Applications

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

Cardiovascular Research
Hypocholesterolemia
Other
      altered fat metabolism

Cell Biology Research
Channel and Transporter Defects

Dermatology Research
Other
      Studies of transepidermal water loss
Skin and Hair Texture Defects

Developmental Biology Research
Perinatal Lethality
      Homozygous
Skin and Hair Texture Defects

Endocrine Deficiency Research
Skin Defects

Metabolism Research
Lipid Metabolism

Neurobiology Research
Alzheimer's Disease
Channel and Transporter Defects
Metabolic Defects

Research Tools
Dermatology Research
Metabolism Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Dhcr24tm1Lex
Allele Name targeted mutation 1, Lexicon Genetics
Allele Type Targeted (Reporter)
Common Name(s) DHCR24-; Dhcr24-; Dhcr24tm1Fein;
Mutation Made By Elena Feinstein,   Quark Biotech, Inc.
Strain of Origin129S5/SvEvBrd
Gene Symbol and Name Dhcr24, 24-dehydrocholesterol reductase
Chromosome 4
Gene Common Name(s) 2310076D10Rik; 3-beta-hydroxysterol delta-24 reductase; 5830417J06Rik; DCE; Nbla03646; RIKEN cDNA 2310076D10 gene; RIKEN cDNA 5830417J06 gene; SELADIN1; mKIAA0018; seladin-1;
Molecular Note The endogenous locus was disrupted by the insertion of a cassette containing lacZ and neo. Transcript was undetected in homozygous mutant mice by Northern blot analysis of RNA obtained from brain and skin tissue. [MGI Ref ID J:87402]

Genotyping

Genotyping Information

Genotyping Protocols

Dhcr24tm1Fein, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Heverin M; Meaney S; Brafman A; Shafir M; Olin M; Shafaati M; von Bahr S; Larsson L; Lovgren-Sandblom A; Diczfalusy U; Parini P; Feinstein E; Bjorkhem I. 2007. Studies on the cholesterol-free mouse: strong activation of LXR-regulated hepatic genes when replacing cholesterol with desmosterol. Arterioscler Thromb Vasc Biol 27(10):2191-7. [PubMed: 17761942]  [MGI Ref ID J:135003]

Kuehnle K; Crameri A; Kalin RE; Luciani P; Benvenuti S; Peri A; Ratti F; Rodolfo M; Kulic L; Heppner FL; Nitsch RM; Mohajeri MH. 2008. Prosurvival effect of DHCR24/Seladin-1 in acute and chronic responses to oxidative stress. Mol Cell Biol 28(2):539-50. [PubMed: 17984220]  [MGI Ref ID J:130231]

Lu X; Kambe F; Cao X; Yoshida T; Ohmori S; Murakami K; Kaji T; Ishii T; Zadworny D; Seo H. 2006. DHCR24-knockout embryonic fibroblasts are susceptible to serum withdrawal-induced apoptosis because of dysfunction of caveolae and insulin-Akt-Bad signaling. Endocrinology 147(6):3123-32. [PubMed: 16513830]  [MGI Ref ID J:129658]

Mirza R; Hayasaka S; Kambe F; Maki K; Kaji T; Murata Y; Seo H. 2008. Increased expression of aquaporin-3 in the epidermis of DHCR24 knockout mice. Br J Dermatol 158(4):679-84. [PubMed: 18241265]  [MGI Ref ID J:169519]

Mirza R; Hayasaka S; Takagishi Y; Kambe F; Ohmori S; Maki K; Yamamoto M; Murakami K; Kaji T; Zadworny D; Murata Y; Seo H. 2006. DHCR24 gene knockout mice demonstrate lethal dermopathy with differentiation and maturation defects in the epidermis. J Invest Dermatol 126(3):638-47. [PubMed: 16410790]  [MGI Ref ID J:106756]

Mirza R; Qiao S; Murata Y; Seo H. 2009. Requirement of DHCR24 for postnatal development of epidermis and hair follicles in mice. Am J Dermatopathol 31(5):446-52. [PubMed: 19542918]  [MGI Ref ID J:169518]

Wechsler A; Brafman A; Shafir M; Heverin M; Gottlieb H; Damari G; Gozlan-Kelner S; Spivak I; Moshkin O; Fridman E; Becker Y; Skaliter R; Einat P; Faerman A; Bjorkhem I; Feinstein E. 2003. Generation of viable cholesterol-free mice. Science 302(5653):2087. [PubMed: 14684813]  [MGI Ref ID J:87402]

Additional References

Dhcr24tm1Lex related

Crameri A; Biondi E; Kuehnle K; Lutjohann D; Thelen KM; Perga S; Dotti CG; Nitsch RM; Ledesma MD; Mohajeri MH. 2006. The role of seladin-1/DHCR24 in cholesterol biosynthesis, APP processing and Abeta generation in vivo. EMBO J 25(2):432-43. [PubMed: 16407971]  [MGI Ref ID J:105158]

Ohyama Y; Meaney S; Heverin M; Ekstrom L; Brafman A; Shafir M; Andersson U; Olin M; Eggertsen G; Diczfalusy U; Feinstein E; Bjorkhem I. 2006. Studies on the transcriptional regulation of cholesterol 24-hydroxylase (CYP46A1): marked insensitivity toward different regulatory axes. J Biol Chem 281(7):3810-20. [PubMed: 16321981]  [MGI Ref ID J:108495]

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 & HusbandryWhen maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings or to C57BL/6J inbred mice (Stock No. 000664). Homozygous mice on the C57BL/6J genetic background die immediately after birth.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2085.00
Animals Provided

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 View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2710.50
Animals Provided

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).

View USA Canada and Mexico Pricing View International Pricing

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
   000664 C57BL/6J
 
  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.
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"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"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "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 the 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 or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

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MICE and PRODUCTS 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.


(6.5)