| Status | Available to order |
| EMMA ID | EM:15993 |
| Citation information | RRID:IMSR_EM:15993 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 | C57BL/6J-Col6a1em1Sal/Cnbc |
| Alternative name | BL/6J- Col6A1em1(c.874G>A) Sal |
| Strain type | Endonuclease-mediated |
| Allele/Transgene symbol | Col6a1em1Sal |
| Gene/Transgene symbol | Col6a1 |
| Provider | Arístides López-Márquez |
| Provider affiliation | Fundació per a la recrea i la docencia Sant Joan de Deu |
| Genetic information | Using CRISPR/Cas9 we have generated a knock-in mouse model that harbors the Col6a1 c.874 G>A; p. G292R mutation. CRISPR technology details: Streptococcus pyogenes Cas9 marketed by IDTDNA was used. The gene encoding Cas9 has not been inserted into the mouse genome. Collagen VI-Related Dystrophies (COL6-RD) are caused by mutations in any of the three major human collagen VI genes (COL6A1, COL6A2, and COL6A3). The majority (around 75%) of mutations are de novo dominant variants (Allamand et al., 2011; Lamandé et al., 2018). Amongst those, glycine to arginine substitutions in the N-terminus of the triple helical collagen domain are common amongst individuals with the intermediate and milder forms of COL6-RD. The mutant alpha chains carrying these glycine substitutions associate with the alpha chains encoded by the wild type allele and are incorporated into tetramers that will be secreted into the extracellular matrix. The tetramers containing mutant chains interfere with the correct assembly and function of the tetramers formed only by wild-type molecules exerting a dominant negative effect and impairing collagen VI microfibril formation and function. Common missense variants in that region of the triple helix are the ones affecting amino acids 284, 290 and 293 (G284R, G290R and G293R substitutions) in exons 9 or 10 of the COL6A1 gene. |
| Phenotypic information | Homozygous:Homozygous mutant mice present compatible symptoms with a myopathic process, including reduced muscle mass, excess deposition of endomysial collagens, as an indication of fibrosis, from an early age, a partial deficit in collagen VI protein levels and localization at the basal lamina, reduced strength and impaired respiratory function.Heterozygous:The phenotype observed is the same as in the case of homozygotes, but milder, with sometimes non-statistical changes observed in some of the parameters and characteristics studied. Even so, they show general features of a myopathic process, as indicated in the case of homozygous individuals. |
| Breeding history | Edited founders were identified by PCR amplification and those carrying the desired alleles were crossed for 5 generations with wild-type C57BL/6J to eliminate possible unwanted off-targets. Heterozygous mice were re-sequenced and crossed with C57BL/6J wild-type animals to generate the B6J-Col6A1em1(c.874G>A) Sal mouse colony. |
| References |
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| Homozygous fertile | yes |
| Homozygous viable | yes |
| Homozygous matings required | no |
| Immunocompromised | no |
| Archiving centre | CNB-CSIC, Centro Nacional de Biotecnologia, Madrid, Spain |
| Animals used for archiving | heterozygous C57BL/6J males |
Orphanet associated rare diseases, based on orthologous gene matching
