B6.Cg-Apoa2tm1Bres Tg(STOP78SER-APOA2)lineK/Orl
| Status | Available to order |
| EMMA ID | EM:14980 |
| Citation information | RRID:IMSR_EM:14980 Research Resource Identifiers (RRID) are persistent unique ID numbers assigned to help researchers cite key resources (e.g. antibodies, model organisms and software projects) in the biomedical literature to improve transparency and reproducibility in research. See https://www.rrids.org/ for more information. |
| International strain name | B6.Cg-Apoa2tm1Bres Tg(STOP78SER-APOA2)lineK/Orl |
| Alternative name | STOP78SER-APOA3 line K |
| Strain type | Transgenic Strains |
| Allele/Transgene symbol | Tg(STOP78SER-APOA2)lineK, Apoa2tm1Bres |
| Gene/Transgene symbol | Tg(STOP78SER-APOA2)lineK, Apoa2 |
Information from provider
| Provider | Athina-Despina Kalopissis |
| Provider affiliation | Centre de Recherche des Cordeliers |
| Genetic information | The normal human APOA2 gene on chromosome 1 is composed of 4 exons and 3 introns and codes for apolipoprotein AII (apoAII), a major protein of HDL (a protective factor against cardiovascular diseases). Normal human apoAII has 77 amino acids, its translation being arrested by a STOP codon after the 77th amino acid. A spontaneous mutation occurred in the STOP codon, transforming it to a serine, and resulted in the formation of a mutated apolipoprotein AII composed of 98 amino acids (described by Yazaki et al., Kidney Int 2001, 60:1658-1665). The variant STOP78SER-ApoAII is an amyloidogenic protein provoking spontaneously dominant hereditary systemic amyloidosis that results in early death (around 45 years of age) due predominantly to renal failure or cardiac dysfunction. To generate an animal model for this life-threatening disease, we constructed the variant STOP78SER-APOA2 gene by site-directed mutagenesis of the 3-kilobase genomic clone of the normal human APOA2 gene (-911/+2045) that includes the endogenous promoter. Details of this procedure are in Supplemental Methods of our article (Chabert et al., Kidney Int. 2019, 96:628-641). |
| Phenotypic information | Homozygous:Homozygous K mice display a plasma concentration of STOP78SER-ApoAII 2 times higher than the physiological level. Amyloid deposition starts spontaneously in 3 to 4-month-old mice and progresses rapidly. K mice die from renal insufficiency from 7 months onwards. Renal glomerular amyloidosis is a major feature of the disease. Important amyloid deposits form in the heart, liver and spleen but also in the stomach, the digestive tract and the adrenal gland. Amyloid was consistently absent in brain, eyes, salivary gland, lung, muscle, testicles and ovaries. Notably, amyloid deposits form in the same organs in K and F mice, albeit they form a little later in life probably depending on the expression level of the amyloidogenic STOP78SER-ApoAII.Heterozygous:Hemizygous K mice display the physiological plasma concentration of STOP78SER-ApoAII. Amyloid deposition starts in 4 to 5-month-old mice and progresses rapidly. K mice die from renal insufficiency from 8 months onwards. Renal glomerular amyloidosis is a major feature of the disease. Important amyloid deposits form in the heart, liver and spleen but also in the stomach, the digestive tract and the adrenal gland. Amyloid was consistently absent in brain, eyes, salivary gland, lung, muscle, testicles and ovaries. Amyloid deposits form in the same organs as in homozygous K mice. |
| Breeding history | The founder mouse obtained by classical transgenesis (microinjection of the transgene into one-cell embryos of (C57BL/6J x CBA/2J)F1 female mice) was mated with C57BL/6 mice to give rise to the K transgenic line. The K line was first backcrossed for up to 10 generations to C57BL/6J strain, and then to the mouse Apoa2 knock-out strain (AII-KO; EMMA strain ID EM:14982) previously backcrossed to the C57BL/6 strain. Tail-derived DNA was subjected to three separate PCRs to identify mice carrying STOP78SER-APOA2 in the AII-KO background. The PCRs revealed: i) the presence of the human STOP78SER-APOA2 gene; ii) the presence of the gene conferring resistance to neomycin (neo gene); iii) the absence of the murine Apoa2 gene. At present all three transgenic lines have been backcrossed into the AII-KO/C57BL/6 background for more than 20 generations. Mice of the K line are crossed with AII-KO mice to obtain hemizygous K mice. The resulting pups are tested by PCR for the presence of human STOP78SER-APOA2. When needed, homozygous K mice are obtained by crossings of hemizygous K mice. These crossings are expected to give 25% homozygous mice, 50% hemizygous mice and 25% AII-KO mice. Homozygosity is assessed by two criteria: i) the STOP78SER-ApoAII serum concentration of the K mouse tested should be 2 times higher than that of the hemizygous mice; ii) when the potentially homozygous K mice are bred with 3 different AII-KO mice, all littermates from the three breedings should be positive for STOP78SER-APOA2 by PCR. |
| References |
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| Homozygous fertile | yes |
| Homozygous viable | yes |
| Homozygous matings required | no |
| Immunocompromised | not known |
Information from EMMA
| Archiving centre | CNRS-TAAM – Typing and Archiving of Animal Models, Orléans, France |
| Animals used for archiving | heterozygous C57BL/6J males |
Disease and phenotype information
Orphanet associated rare diseases, based on orthologous gene matching
- AApoAII amyloidosis / Orphanet_238269
Literature references
- A transgenic mouse model reproduces human hereditary systemic amyloidosis.;Chabert Michèle, Rousset Xavier, Colombat Magali, Lacasa Michel, Kakanakou Hermine, Bourderioux Mathilde, Brousset Pierre, Burlet-Schiltz Odile, Liepnieks Juris J, Kluve-Beckerman Barbara, Lambert Gilles, Châtelet François P, Benson Merrill D, Kalopissis Athina D, ;2019;Kidney international;96;628-641; 31200944