Strain Name: |
B6.129X1-Apobtm1.1Zc/J |
|---|---|
Stock Number: |
007682 |
Availability: | Repository- Live |
General Terms and Conditions |
| Genes & Alleles | Apob; Apobtm1.1Zc; |
Product Information
Strain Details
Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Targeted Mutation Mating System +/+ sibling x Heterozygote (Female x Male) Species laboratory mouse Donating Investigator Gustav Schonfeld, Washington University School of Medicine Generation N9+ (14-MAR-08) Strain Description
Mice homozygous for this apoB38.9 allele (apoB38.9/38.9) are viable with impaired fertility, bearing a premature stop codon at residue 1767 of the targeted gene. As a result, homozygous plasma shows a truncated apoB38.9 as the sole apoB protein. Plasma from heterozygous (apoB+/38.9) mice have reduced apoB100 and apoB48 compared to wildtype, with apoB38.9 representing 20% of total circulating apoB. This apoB38.9 truncation affects both apoB100 and apoB48 metabolism in mice, and mimics human Familial Hypobetalipoproteinemia (FHBL). Homozygous and, to a lesser extent, heterozygous mice exhibit symptoms of FHBL due to impaired lipoprotein export system/VLDL secretion, including elevated hepatic triglyceride (TG), cholesterol and free fatty acids (FFA), with decreased plasma TG and cholesterol. Because plasma and liver lipid profiles range from mild to severe in populations of heterozygous apoB38.9 mice on a mixed (C57BL/6J;129X1/SvJ) genetic background, apoB+/38.9 congenic mice were generated on three different inbred strains with characterized differences in liver fat: SWR/J (low liver TG strain, ~40mg/dL), C57BL/6J (medium liver TG, ~140mg/dL), and BALB/cByJ (high liver TG strain, ~200 mg/dL). All three apoB+/38.9 congenic strains exhibit significantly impaired hepatic TG secretion compared to their respective genetic backgrounds, with significant interactions observed between genetic background and apoB genotype for liver TG and FFA. BALB/cByJ-apoB38.9 mice (Stock No. 007683) exhibit the greatest hepatic TG and FFA increase (probably due to elevated hepatic TG synthesis rate). Despite having the lowest degree of hepatic steatosis among the three apoB+/38.9 congenic strains, SWR/J-apoB38.9 mice (Stock No. 007679) show insulin resistance, with BALB/cByJ-apoB38.9 mice exhibiting intermediate and C57BL/6J-apoB38.9 mice (Stock No. 007682) exhibiting the greatest insulin resistance. Additional comparisons between the three congenic strains reveal that C57BL/6J-apoB38.9 mice have significant increase of fatty acid synthesis rate compared to the other two congenic strains, while SWR/J-apoB38.9 mice show dynamic feedback regulation of fatty acids and TG synthesis and beta-oxidation in response to excessive hepatic TG accumulation. Gender dimorphism is observed; while BALB/cByJ-apoB38.9 males have reduced plasma cholesterol levels compared to wildtype males, females from all three apoB+/38.9 congenic strains have reduced plasma cholesterol compared to wildtype females. Male BALB/cByJ-apoB38.9 and C57BL/6J-apoB38.9 mice have significant reduction of liver TG synthesis compared to wildtype males, while SWR/J-apoB38.9 females show the same significant reduction. These apoB38.9 mutant mice may be useful to study the genetic and molecular mechanism of apoB defects and lipid metabolism/liver fat accumulation, the relationship between hepatic steatosis and insulin resistance, the progression of advanced non-alcoholic fatty liver diseases (NAFLD), and atherosclerosis. These apoB38.9 mutant mice may also be useful in conjunction with other apoB mutant mice, including Stock No. 002053 (apoB70), Stock No. 002876 (apoB48-only), and Stock No. 002877 (apoB100-only).Strain Development
A targeting vector was designed (by site-directed mutagenesis) to delete nucleotide 5449 of the mouse apo B cDNA sequence (the deletion is predicted to produce a premature stop codon at the same position (i.e. residue 1767) as that occurring in the apo B-38.9 mutation of human familial hypobetalipoproteinemia (FHBL) subjects). This also inserted a loxP-flanked PGK-neo cassette within intron 24. The construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a cre-expressing vector to remove the selection cassette (leaving a single loxP site in intron 24) and then injected into C57BL/6 blastocysts. The resulting chimeric males were bred to C57BL/6 females. Heterozygotes were then backcrossed to C57BL/6J inbred mice (see Stock No. 000664) for 8 generations prior to arrival at The Jackson Laboratory.
Related Disease (OMIM) Terms |
Mammalian Phenotype Terms assigned by genotype |
Gene & Allele Details
| Allele Symbol | Apobtm1.1Zc | ||
|---|---|---|---|
| Allele Name | targeted mutation 1.1, Zhouji Chen | ||
| Common Name(s) | apoB38.9; | ||
| Mutation Made By | Zhouji Chen, Washington University School of Medicine | ||
| Strain of Origin | 129X1/SvJ | ||
| ES Cell Line Name | RW-4 | ||
| ES Cell Line Strain | 129X1/SvJ | ||
| Gene Symbol and Name | Apob, apolipoprotein B | ||
| Chromosome | 12 | ||
| Gene Common Name(s) | AI315052; Aa1064; Ac1-060; ApoB-100; ApoB-48; FLDB; expressed sequence AI315052; | ||
| Molecular Note | Deletion of nucleotide 5449 in exon 26 and a loxP-flanked PGK-neo cassette inserted into intron 24 were introduced to the gene via homologous recombination. This deletion mimics the ApoB-38.9 truncation mutation found in human familial hypobetalipoproteinemia (FHBL). The neo cassette was removed by transient expression of Cre recombinase in correctly targeted ES cells. Southern blot analysis confirmed the absence of the neo cassette in homozygous mutant mice; Western blot analysis showed a mutant proteinproduct of similar size to the human ApoB-38.9 mutant protein. [MGI Ref ID J:65191] | ||
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Colony Maintenance
| Breeding & Husbandry | When maintaining a live colony, heterozygotes are bred to wildtype siblings or to C57BL/6J inbred mice (see Stock No. 000664). The donating investigator reports that homozygous mice are produced in reduced rates and are probably infertile. |
|---|---|
| Diet Information | LabDiet® 5K52/5K67 |
Related Strains
Strains carrying Apobtm1.1Zc allele
007683 CByJ.129X1(Cg)-Apobtm1.1Zc/J 007679 SWR.129X1(B6)-Apobtm1.1Zc/J View Strains carrying Apobtm1.1Zc (2 strains)
002053 B6.129P2-Apobtm1Unc/J 002878 B6;129-Apobtm1Sgy Apoetm1Unc/J 002879 B6;129-Apobtm2Sgy Apoetm1Unc/J 002876 B6;129S-Apobtm1Sgy/J 003000 B6;129S-Apobtm2Sgy Ldlrtm1Her/J 002877 B6;129S7-Apobtm2Sgy/J 004192 STOCK Mttptm2Sgy Ldlrtm1Her Apobtm2Sgy Tg(Mx1-cre)1Cgn/J
Additional Web Information
Congenic Nomenclature
Animal Health Reports
Room Number AX12
Research Applications
This mouse can be used to support research in many areas including:
Cardiovascular Research
Atherosclerosis
Hypercholesterolemia
Hypertriglyceridemia
Hypocholesterolemia
Hypotriglyceridemia
Other (altered fat metabolism)
Other (altered lipoprotein profile)
Diabetes and Obesity Research
Insulin Resistance
Internal/Organ Research
Liver Defects
Metabolism Research
Lipid Metabolism
Mouse/Human Gene Homologs
hypobetalipoproteinemia, familial
Reproductive Biology Research
Fertility Defects
Research Tools
Cardiovascular Research
Diabetes and Obesity Research
Internal/Organ Research
Metabolism Research
References
Selected Reference(s)
Additional ReferencesChen Z; Fitzgerald RL; Averna MR; Schonfeld G. 2000. A targeted apolipoprotein B-38.9-producing mutation causes fatty livers in mice due to the reduced ability of apolipoprotein B-38.9 to transport triglycerides J Biol Chem 275(42):32807-15. [PubMed: 10893242] [MGI Ref ID J:65191]
Price and Supply Information
| Strain Name: | B6.129X1-Apobtm1.1Zc/J |
| Stock Number: | 007682 |
Price Details
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
|---|---|
| Supply Notes |
Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. |
| Licensing | See General Terms and Conditions below for Licensing and Use Restrictions |
| Control Information | View Control Information in Strain Details. |
General Terms and Conditions
View JAX® Mice & Services Conditions of Use.
Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.
For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
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 and Purchasing Information
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