Name: transgene insertion 1, Ming-Ling Chang
Alteration at locus: Transgenic
Promoter: tetO (Synthetic)
Name: tetracycline operon
Alteration at locus: Transgenic
ES Cell Line: Not Applicable
Homozygous phenotype:Not evaluated
Hemizygous transgenic phenotype: To mimic hepatitis C infection in humans, Tg(tetO-HCV)1Mlch hemizygotes are bred to mice expressing the Cebpb-tTA (LaptTA) transgene and maintained on doxycycline through weaning to replicate the timing of hepatitis C infection in humans. Following withdrawal of doxycycline (dox), 50 to 60% of hepatocytes express the HCV core; expression is localized to the cytoplasmic vesicle membrane. HCV-positive hepatocytes are distributed randomly within the liver lobules. Expression is not detected in any of the other tissues tested. Mice do not exhibit significant hepatic inflammation although aminotransferase levels are elevated at one month after dox withdrawal. Hepatic steatosis is observed at two months of age; initially appearing as prominent microvesicular steatosis the pattern evolves to low-level macrovesicular steatosis paralleling the reduction in HCV-core expressing hepatocytes that occurs over time. This mutant mouse strain may be useful in studies of hepatic steatosis and hepatitis C infection.
Strain genetic background: C57BL/6; NRMI; FVB/N
Strain Development: The tetO-HCV transgene contains sequence from hepatitis C virus (HCV) core derived from the plasma of an infected patient and cloned into a vector containing a tetracycline response element (TRE). The construct was microinjected into FVB/N fertilized ova. Founder lines were established and crossed to mice carrying the Tg(Cebpb-tTA)5Bjd (also know as LaptTA) transgene on a mixed NMRI, FVB/N and C57BL/6 background. Upon arrival, the Tg(Cebpb-tTA)5Bjd transgene was bred out of the strain.
Suggested Control Mice: Wild-ype littermates
Donor: Robert Farese, Ph.D., Gladstone Institutes
Chang ML; Chen JC; Yeh CT; Sheen IS; Tai DI; Chang MY; Chiu CT; Lin DY; Bissell DM, Topological and evolutional relationships between HCV core protein and hepatic lipid vesicles: studies in vitro and in conditionally transgenic mice., World J Gastroenterol 2007 Jul 7;13(25):3472-7 (Medline PMID: 17659694)
When maintaining a live colony, mice hemizygous for the transgene may be bred together or to wildtype siblings.
Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at firstname.lastname@example.org for more details.
The donor or their institution limits the distribution to non-profit institutions only.
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.
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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.
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