The donating investigator reports that homozygous females are sterile, homozygous males are subfertile. The phenotype of the Fance mutants resembles the phenotype of other Fanconi anemia mutations in mice. Mouse model for Fanconi anemia. Studies of genome stability and DNA damage repair.
Paul A Overbeek, Baylor College of Medicine
Genetic Background | Generation |
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Allele Type |
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Transgenic (Null/Knockout, Inserted expressed sequence) |
The donating investigator reports that homozygous females are sterile, homozygous males are subfertile. The phenotype of the Fance mutants resembles the phenotype of other Fanconi anemia mutations in mice. Mouse model for Fanconi anemia. Studies of genome stability and DNA damage repair.
A lentiviral transgenic approach was used to generate these mice. The Tyro-IRES-sd-loxP-FUGW lentiviral transgene (LV2187) was designed with a mouse tyrosinase minigene (Tyro) followed by an IRES::3xATG::splice-donor::loxP sequence in the FUGW self-inactivating HIV-based lentiviral vector backbone. The Tyro-IRES-sd-loxP replaced the ubiquitin-c promoter, EGFP, and WPRE sequences originally found in the FUGW lentiviral vector. The Tyro minigene is composed of the mouse Tyr enhancer region (623 bp), promoter region (657 bp), and 1566 bp cDNA sequence (including the stop codon); all in antisense orientation relative to the FUGW backbone. The Tyro minigene is followed by an internal ribosome entry site (IRES) ending with ATGs in all three reading frames (3xATG), an artificial splice donor sequence, and a loxP site in this construct. This packaged lentivirus was injected subzonally (under the zona pellucida) into 1 cell stage FVB/N mouse embryos. Expression of the tyrosinase minigene results in melanin synthesis, so founder mice (F0) were identified by inspection for pigmentation. All F0 mice exhibited mosaic pigmentation. Most F0 mice had more than one lentiviral integration site. F0 mice were assigned an OVE number and then bred with FVB/N mice. Pigmented offspring (F1) with different coat colors were designated as subline A, B, C, etc., for each family. F1 mice were bred with FVB/N mice. F2 mice with different coat colors were designated as sublines A-1, A-2, etc., or B-1, B-2, etc. Breeding with FVB/N mice was continued until litters with only one or two different coat colors were obtained. Mice with identical coat colors were then inbred and assessed for the presence or absence of viable homozygotes. Hemizygous mice of line OVE 2364E-2a2 exhibit a light grey coat color. Using inverse PCR analysis, the lentiviral integration site was identified in intron 8 of the Fanconi anemia E gene (Fance) on chromosome 17. The 3'-LTR is linked to the (+) strand of DNA at position 28,458,210 bp [NCB137/mm9; 3'-28,458,210(+)].
Expressed Gene | Tyr, tyrosinase, mouse, laboratory |
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Site of Expression |
Allele Name | transgene insertion 2364E-2a2, Paul Overbeek |
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Allele Type | Transgenic (Null/Knockout, Inserted expressed sequence) |
Allele Synonym(s) | FanceTg(Tyr)OVE2364E-2a2Chfu |
Gene Symbol and Name | Fance, Fanconi anemia, complementation group E |
Gene Synonym(s) | |
Promoter | Tyr, tyrosinase, mouse, laboratory |
Expressed Gene | Tyr, tyrosinase, mouse, laboratory |
Strain of Origin | FVB/N |
Chromosome | 17 |
Molecular Note | The Tyrosinase minigene is composed of the mouse Tyr enhancer region (623 bp), promoter region (657 bp), and 1566 bp cDNA sequence (including the stop codon). The Tyro minigene is followed by an internal ribosome entry site (IRES) ending with ATGs in all three reading frames (3xATG), an artificial splice donor sequence, and a loxP site. Using inverse PCR analysis, the lentiviral integration site was identified in intron 8 of the Fanconi anemia E gene (Fance) on chromosome 17. The 3'-LTR is linked to the (+) strand of DNA at position 28,458,210 bp [NCB137/mm9; 3'-28,458,210(+)]. |
Homozygous females are sterile. Homozygous males are subfertile. The donating investigator mates omozygous males to heterozygous females.
When using the FVB/N-FanceTg(Tyr)2364E-2a2Ove/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36526 in your Materials and Methods section.
Facility Barrier Level Descriptions
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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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