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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
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Description
Strain Information
Former Names B6.129S4-Ncb5ortm1Hfb/HfbJ (Changed: 29-SEP-05 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129S4 Generation N10p (29-MAY-05) Donating Investigator H. Bunn, Brigham and Womens Hospital Appearance
black
Related Genotype: a/aDescription
Mice heterozygous for the targeted mutation are viable and fertile, glucose tolerant, have normal blood sugar levels, serum lipid profiles and white adipose tissue mass.No protein from the targeted gene was detected by Western Blot analysis of mice homozygous for the allele. Homozygous mice consume more food, have decreased adipose tissue mass and are hyperlipidemic compared to wildtype controls post-weaning. At 4 weeks of age glucose levels are normal but insulin levels are 40% of wildtype controls. At 7 weeks of age clinical diabetes is present in both male and female of homozygous mice. Histological evaluation of pancreas from 21 week old homozygote animals revealed a significant reduction in the number of islets and decreased cytoplasmic to nuclear ratio in the islet cells and there was no insulitis nor phagocytosis of necrotic beta cell fragments. While there is a progressive loss of beta cells in aging homozygous mice, there is no loss of alpha, delta or PP cells. Electron microscopy reveals degranulated beta cells and hypertrophic and hyperplastic mitochodria.
This strain is useful in islet transplantation research, stem cell research and as a tool for studying the role of oxidative stress in diabetes.
Development
A construct containing a hygromycin expression cassette replaces a region extending from the 3' end of exon 3 to the 5' end of intron 4 of Cyb5r4 (cloned from a 129/Sv mouse), deleting exon 4 the heme binding domain crucial to enzyme stability and biochemical properties, was transfected into 129S4/SvJae embryonic stem cells (ES cells). These ES cells were injected into C57BL/6 blastocysts. Chimeric founders were mated to C57BL/6 and subsequently intercrossed to generate homozygotes. In 2005, the Type 1 Diabetes Resource received heterozygous B6.129S4-Cyb5r4tm1Hfb/HfbJ at generation N9.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying Cyb5r4tm1Hfb allele
005516 C.129S4-Cyb5r4tm1Hfb/HfbJ View Strains carrying Cyb5r4tm1Hfb (1 strain)
Additional Web Information
Congenic Nomenclature
Phenotype
Phenotype Information
Diabetes Mellitus, Noninsulin-Dependent; NIDDM - Models with phenotypic similarity to human disease where etiologies are distinct.2
2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Cyb5r4tm1Hfb/Cyb5r4tm1Hfb
involves: 129S4/SvJae * BALB/cAnN
- homeostasis/metabolism phenotype
- abnormal glucose homeostasis (MGI Ref ID J:91486)
- decreased circulating insulin level (MGI Ref ID J:91486)
- insulin levels 40% of normal at 4 weeks of age
- insulin levels 25% normal at 7 weeks of age and barely detectable after fasting
- impaired glucose tolerance (MGI Ref ID J:91486)
- impaired tolerance for glucose given ip at 4 weeks of age
- increased circulating glucose level (MGI Ref ID J:91486)
- normal glucose levels at 4 weeks of age in a fed state
- by 7 weeks of age blood glucose is 3X normal in the fed state or after overnight fasting
- increased insulin sensitivity (MGI Ref ID J:91486)
- insulin tolerance is normal but with a slight increase in insulin sensitivity
- hyperlipidemia (MGI Ref ID J:91486)
- endocrine/exocrine gland phenotype
- abnormal islet of Langerhans morphology (MGI Ref ID J:91486)
- decreased cytoplasm to nuclear ratio in islet cells
- no inflammatory cells or necrotic beta cells
- cell distribution pattern normal at 4 weeks of age
- decreased pancreatic beta cell number (MGI Ref ID J:91486)
- beta cell numbers decreased at 7 weeks of age
- at 21 weeks a very small number of beta cells are left
- increased size and number of mitochondria
- decreased insulin secretion (MGI Ref ID J:91486)
- early defect in glucose stimulated insulin secretion but not in glucose sensing pathway
- adipose tissue phenotype
- decreased adipose tissue amount (MGI Ref ID J:91486)
- decreased adipose tissue mass
- behavior/neurological phenotype
- abnormal eating behavior (MGI Ref ID J:91486)
- increased food intake
- digestive/alimentary phenotype
- abnormal islet of Langerhans morphology (MGI Ref ID J:91486)
- decreased cytoplasm to nuclear ratio in islet cells
- no inflammatory cells or necrotic beta cells
- cell distribution pattern normal at 4 weeks of age
- decreased pancreatic beta cell number (MGI Ref ID J:91486)
- beta cell numbers decreased at 7 weeks of age
- at 21 weeks a very small number of beta cells are left
- increased size and number of mitochondria
- decreased insulin secretion (MGI Ref ID J:91486)
- early defect in glucose stimulated insulin secretion but not in glucose sensing pathway
This mouse can be used to support research in many areas including:
Diabetes and Obesity Research
Hyperglycemia
Hypoinsulinemia
Impaired Insulin Processing
Insulin Receptors and Growth Factors
Islet Transplantation Studies
Type 1 Diabetes (IDDM) (MODY, mature onset diabetes of the young)
Endocrine Deficiency Research
Pancreas Defects
Metabolism Research
Lipid Metabolism
Research Tools
Apoptosis Research
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Cyb5r4tm1Hfb | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, H Franklin Bunn | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Ncb5or-; | ||
| Mutation Made By | H. Bunn, Brigham and Womens Hospital | ||
| Strain of Origin | 129S4/SvJae | ||
| Gene Symbol and Name | Cyb5r4, cytochrome b5 reductase 4 | ||
| Chromosome | 9 | ||
| Gene Common Name(s) | 2810034J18Rik; B5+B5R; C79736; NADPH cytochrome B5 oxidoreductase; NCB5OR; Ncb5or; RIKEN cDNA 2810034J18 gene; RP4-676J13.1; b5&b5R; b5/b5r; dJ676J13.1; expressed sequence C79736; | ||
| Molecular Note | Exon 4, which contains sequence encoding the heme-binding domain, was replaced with a PGK-hygromycin gene. Mutant mice did not express full length mRNA or protein, as shown by Northern blot and Western blot, respectively. [MGI Ref ID J:91486] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Cyb5r4tm1Hfb, SEP PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Xie J; Zhu H; Larade K; Ladoux A; Seguritan A; Chu M; Ito S; Bronson RT; Leiter EH; Zhang CY; Rosen ED; Bunn HF. 2004. Absence of a reductase, NCB5OR, causes insulin-deficient diabetes. Proc Natl Acad Sci U S A 101(29):10750-5. [PubMed: 15247412] [MGI Ref ID J:91486]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
Additional Supply Details
| Pricing for International shipping destinations |
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*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
General Terms and Conditions
See Terms of Use
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