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| These Dhcr7Ex8 mutant mice may be useful in studying Smith-Lemli-Opitz/RSH Syndrome (SLOS; a birth-defect mental-retardation syndrome) or other metabolic disorders involved with cholesterol biosynthesis. | |||||||||||||||
- 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 Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N9+N1F2pN1
Generation DefinitionsDonating Investigator Shailendra B Patel, Medical College of Wisconsin Description
Mice homozygous for the Dhcr7Ex8 allele lack the exon 8 coding sequence and flanking splice acceptor site of the targeted gene, resulting in the truncated DHCR7 mutation most frequently observed in Smith-Lemli-Opitz/RSH Syndrome (SLOS) patients (IVS8-1G > C). Although a truncated product is transcribed from the targeted gene, no mRNA containing the deleted 3'-coding region is detected in homozygous liver or brain tissue. Homozygous mice exhibit the same biochemical defects as observed with SLOS patients, including markedly reduced tissue cholesterol and total sterol levels, and 30- to 40-fold elevated concentrations of 7-dehydrocholesterol. Newborn homozygotes have difficulty breathing, do not suckle, and die soon after birth with immature lungs, enlarged bladder, and, frequently, cleft palate. These Dhcr7Ex8 mutant mice may be useful in studying Smith-Lemli-Opitz/RSH Syndrome (SLOS; a birth-defect mental-retardation syndrome) or other metabolic disorders involved with cholesterol biosynthesis.Development
A targeting vector containing a neomycin resistance gene was used to disrupt exon 8. The construct was electroporated into 129P2/OlaHsd derived E14TG2a embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The mice were then bred to mice carrying the Apoetm1Unc allele (on a C57BL/6J congenic background), and then backcrossed to C57BL/6 for 8 generations prior to arriving at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J to remove the Apoetm1Unc allele. These mice carry only the Dhcr7Ex8 mutant allele (also called Dhcr7tm1Gst).
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
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Phenotype
Phenotype Information
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Smith-Lemli-Opitz Syndrome; SLOS
assigned by genotype
Dhcr7tm1Gst/Dhcr7tm1Gst
B6.129P2-Dhcr7tm1Gst
- mortality/aging
- complete neonatal lethality
- die within 24 hours and most within 14 hours of birth (MGI Ref ID J:93296)
- growth/size phenotype
- decreased birth body size
- at birth (MGI Ref ID J:93296)
- fetal growth retardation
- growth retardation beginning at E14.5-E16.5 (MGI Ref ID J:93296)
- respiratory system phenotype
- abnormal breathing pattern
- breathing is irregular and shallow (MGI Ref ID J:93296)
- abnormal lung morphology (MGI Ref ID J:93296)
- abnormal lung development
- lungs exhibit delayed differentiation of type I alveolar epithelial cells (AEC), however differentiation of type II AECs is normal (MGI Ref ID J:93296)
- abnormal lung saccule morphology
- lungs show varying severity of impaired pre-alveolar development, including delayed saccular development from E17.5 onwards (MGI Ref ID J:93296)
- abnormal lung epithelium morphology
- lungs exhibit delayed expansion of epithelial tubules (MGI Ref ID J:93296)
- abnormal type I pneumocyte morphology
- lungs exhibit a delay in differentiation of type I alveolar epithelial cells (AEC) as indicated by fewer flattened type I cells annd reduced expression of type I AEC markers (MGI Ref ID J:93296)
- abnormal lung vasculature morphology
- marker analysis indicates a delay in lung vascular development, with an undeveloped pulmonary capillary bed at E20.5 (MGI Ref ID J:93296)
- abnormal pulmonary alveolus morphology
- abnormal type I pneumocyte morphology
- lungs exhibit a delay in differentiation of type I alveolar epithelial cells (AEC) as indicated by fewer flattened type I cells annd reduced expression of type I AEC markers (MGI Ref ID J:93296)
- small lung (MGI Ref ID J:93296)
- behavior/neurological phenotype
- no spontaneous movement
- lack of spontaneous movement in newborns (MGI Ref ID J:93296)
- cardiovascular system phenotype
- abnormal lung vasculature morphology
- marker analysis indicates a delay in lung vascular development, with an undeveloped pulmonary capillary bed at E20.5 (MGI Ref ID J:93296)
- homeostasis/metabolism phenotype
- abnormal lipid level
- total sterols at birth are reduced in lungs by about 30% (MGI Ref ID J:93296)
- decreased cholesterol level
- cholesterol content in lungs remains at almost constant low levels between E13.5 and P0 instead of increasing as in controls (MGI Ref ID J:93296)
- increased circulating corticosterone level
- plasma corticosterone levels in P0 mutants is increased by about 40% (MGI Ref ID J:93296)
- hypoxia (MGI Ref ID J:93296)
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Dhcr7tm1Gst/Dhcr7tm1Gst
involves: 129P2/OlaHsd
- mortality/aging
- complete neonatal lethality
- homeostasis/metabolism phenotype
- abnormal cholesterol homeostasis
- abnormal enzyme/ coenzyme level
- levels of HMG-CoA reductase protein are reduced (MGI Ref ID J:71611)
- abnormal enzyme/coenzyme activity
- HMG-CoA reductase activities are reduced 6-fold in the liver and 2.7-fold in brain microsomes (MGI Ref ID J:71611)
- abnormal lipid level
- decrease in total sterol levels in the brain and liver (MGI Ref ID J:71611)
- respiratory system phenotype
- abnormal lung morphology
- compact lungs with sparse, unconnected air spaces (MGI Ref ID J:71611)
- abnormal lung development
- lungs of newborns are similar in appearance to normal 15- to 16-gestational day mice, suggesting that lungs may be immature (MGI Ref ID J:71611)
- impaired lung alveolus development
- at E19.5, saccular formation is absent with the failure of pre-alveolar septae thinning and development of sac spaces unlike in wild-type mice (MGI Ref ID J:141730)
- respiratory failure (MGI Ref ID J:71611)
- behavior/neurological phenotype
- hypoactivity
- lack movement shortly after birth (MGI Ref ID J:71611)
- no suckling reflex
- none of the pups suckle (MGI Ref ID J:71611)
- growth/size phenotype
- decreased birth weight (MGI Ref ID J:71611)
- renal/urinary system phenotype
- distended urinary bladder
- 90% exhibit greatly distended urinary bladder (MGI Ref ID J:71611)
- craniofacial phenotype
- cleft secondary palate
- 12% exhibit cleft palate (MGI Ref ID J:71611)
- digestive/alimentary phenotype
- cleft secondary palate
- 12% exhibit cleft palate (MGI Ref ID J:71611)
- liver/biliary system phenotype
- decreased liver cholesterol level
- decrease in cholesterol levels in liver (MGI Ref ID J:71611)
This mouse can be used to support research in many areas including:
Cardiovascular Research
Metabolic Syndrome
Other
altered fat metabolism
altered lipoprotein profile
Developmental Biology Research
Perinatal Lethality
Homozygous
Metabolism Research
Enzyme Deficiency
Lipid Metabolism
Research Tools
Metabolism Research
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Dhcr7tm1Gst | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, G S Tint | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Dhcr7-; Dhr7delEx8; | ||
| Mutation Made By | Hongwei Wu, Medical College of Wisconsin | ||
| Strain of Origin | 129P2/OlaHsd | ||
| ES Cell Line Name | E14TG2a | ||
| ES Cell Line Strain | 129P2/OlaHsd | ||
| Gene Symbol and Name | Dhcr7, 7-dehydrocholesterol reductase | ||
| Chromosome | 7 | ||
| Gene Common Name(s) | AA409147; SLOS; expressed sequence AA409147; | ||
| Molecular Note | A mutation commonly found in human Smith-Lemli-Opitz/RSH syndrome (SLOS) was mimicked in mouse by replacement of exon 8 and the flanking regions with a PGK-neo cassette in the reverse orientation. The mutation results in deletion of 1/3 of the protein from amino acids 318-471. RT-PCR analysis of liver mRNA from homozygous mutant animals did not amplify a product using primers to the 3' end of the gene. Western blot analysis using antibodies recognizing residues 454-467 of the human protein did not detectprotein product in liver proteins from homozygous mutants. [MGI Ref ID J:71611] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Dhcr7tm1Gst, Standard PCR
Dhcr7tm1Gst, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Fitzky BU; Moebius FF; Asaoka H; Waage-Baudet H; Xu L; Xu G; Maeda N; Kluckman K; Hiller S; Yu H; Batta AK; Shefer S; Chen T; Salen G; Sulik K; Simoni RD; Ness GC; Glossmann H; Patel SB; Tint GS. 2001. 7-Dehydrocholesterol-dependent proteolysis of HMG-CoA reductase suppresses sterol biosynthesis in a mouse model of Smith-Lemli-Opitz/RSH syndrome. J Clin Invest 108(6):905-15. [PubMed: 11560960] [MGI Ref ID J:71611]
Solca C; Pandit B; Yu H; Tint GS; Patel SB. 2007. Loss of apolipoprotein E exacerbates the neonatal lethality of the Smith-Lemli-Opitz syndrome mouse. Mol Genet Metab 91(1):7-14. [PubMed: 17197219] [MGI Ref ID J:121454]
Additional References
Dhcr7tm1Gst relatedMatabosch X; Rahman M; Hughes B; Patel SB; Watson G; Shackleton C. 2009. Steroid production and excretion by the pregnant mouse, particularly in relation to pregnancies with fetuses deficient in Delta7-sterol reductase (Dhcr7), the enzyme associated with Smith-Lemli-Opitz syndrome. J Steroid Biochem Mol Biol 116(1-2):61-70. [PubMed: 19406241] [MGI Ref ID J:152110]
Moy SS; Nadler JJ; Young NB; Nonneman RJ; Grossman AW; Murphy DL; D'Ercole AJ; Crawley JN; Magnuson TR; Lauder JM. 2009. Social approach in genetically engineered mouse lines relevant to autism. Genes Brain Behav 8(2):129-42. [PubMed: 19016890] [MGI Ref ID J:151144]
Tint GS; Yu H; Shang Q; Xu G; Patel SB. 2006. The use of the Dhcr7 knockout mouse to accurately determine the origin of fetal sterols. J Lipid Res 47(7):1535-41. [PubMed: 16651660] [MGI Ref ID J:112056]
Waage-Baudet H; Dunty WC Jr; Dehart DB; Hiller S; Sulik KK. 2005. Immunohistochemical and microarray analyses of a mouse model for the smith-lemli-opitz syndrome. Dev Neurosci 27(6):378-96. [PubMed: 16280635] [MGI Ref ID J:103328]
Waage-Baudet H; Lauder JM; Dehart DB; Kluckman K; Hiller S; Tint GS; Sulik KK. 2003. Abnormal serotonergic development in a mouse model for the Smith-Lemli-Opitz syndrome: implications for autism. Int J Dev Neurosci 21(8):451-9. [PubMed: 14659996] [MGI Ref ID J:100040]
Xu L; Mirnics K; Bowman AB; Liu W; Da J; Porter NA; Korade Z. 2012. DHCEO accumulation is a critical mediator of pathophysiology in a Smith-Lemli-Opitz syndrome model. Neurobiol Dis 45(3):923-9. [PubMed: 22182693] [MGI Ref ID J:182044]
Yu H; Li M; Tint GS; Chen J; Xu G; Patel SB. 2007. Selective reconstitution of liver cholesterol biosynthesis promotes lung maturation but does not prevent neonatal lethality in Dhcr7 null mice. BMC Dev Biol 7:27. [PubMed: 17408495] [MGI Ref ID J:141730]
Yu H; Wessels A; Chen J; Phelps AL; Oatis J; Tint GS; Patel SB. 2004. Late gestational lung hypoplasia in a mouse model of the Smith-Lemli-Opitz syndrome. BMC Dev Biol 4(1):1. [PubMed: 15005800] [MGI Ref ID J:93296]
Yu H; Wessels A; Tint GS; Patel SB. 2005. Partial rescue of neonatal lethality of Dhcr7 null mice by a nestin promoter-driven DHCR7 transgene expression. Brain Res Dev Brain Res 156(1):46-60. [PubMed: 15862627] [MGI Ref ID J:98266]
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 are bred to wildtype siblings or to C57BL/6J inbred mice. Homozygotes have abnormalities leading to perinatal death.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
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 | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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.Ordering Information
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