B6.Cg-Apoa2tm1Bres Tg(APOA2*S78)Y/Orl
| Status | Available to order |
| EMMA ID | EM:14981 |
| Citation information | RRID:IMSR_EM:14981 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(APOA2*S78)Y/Orl |
| Alternative name | STOP78SER-APOA4 line Y |
| Strain type | Transgenic Strains |
| Allele/Transgene symbol | Tg(APOA2*S78)Y, Apoa2tm1Bres |
| Gene/Transgene symbol | Tg(APOA2*S78)Y, 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:Line Y homozygous mice display a plasma concentration of the APOII Ser78-STOP transgene, two times lower than the physiological level. This low expression level does not cause amyloidosis in any organ, even in 15 months old mice. Thus, homozygous line Y mice serve as a negative control in all studies. The two times lower than normal plasma concentration of the APOII Ser78-STOP transgene may correspond to the limit of its amyloidogenic potential.Heterozygous:Line Y hemizygous mice display a plasma concentration of the APOII Ser78-STOP transgene, four times lower than the physiological level. This very low expression level does not cause amyloidosis in any organ, even in 15 months old mice. Hemizygous line Y mice have not been used in studies because of the very low expression level of the transgene. |
| 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 Y transgenic line. The Y line was first backcrossed for up to 10 generations to C57BL/6J strain, and then to the mouse Apoa2 knock-out strain (EMMA strain ID EM:14982) previously backcrossed to C57BL/6. Tail-derived DNA was subjected to three separate PCRs to identify mice carrying STOP78SER-APOA2 in the Apoa2 knock-out 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 Apoa2 knock-out/C57BL/6 background for more than 20 generations. Y mice are systematically inbred because they are used only in the homozygous state. Indeed, in the homozygous state their plasma concentration of amyloidogenic human APOA2 is two times lower than the physiological level. This shows the approximate limit of the amyloidogenic potential of this abnormal protein. |
| References |
|
| Homozygous fertile | yes |
| Homozygous viable | yes |
| Homozygous matings required | yes |
| 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