MGI phenotypes (gene matching)
B6.129(C)-Mir10atm1.1Ahl/Kctt
| Status | Available to order |
| EMMA ID | EM:08495 |
| International strain name | B6.129(C)-Mir10atm1.1Ahl/Kctt |
| Alternative name | miR-10a KO |
| Strain type | Targeted Mutant Strains : Knock-out |
| Allele/Transgene symbol | Mir10atm1.1Ahl |
| Gene/Transgene symbol | Mir10a |
Information from provider
| Provider | Anders Lund |
| Provider affiliation | Pr. Anders Lund, Biotech Research and Innovation Centre, University of Copenhagen |
| Genetic information | A null allele of miR-10a was generated by gene targeting, consisting of the replacement of the 70 central nucleotides of the pre-miRNA sequence of miR-10a for a loxP-flanked neo selection cassette. Breeding of miR-10a +/neo mice to a mouse strain holding an ubiquitously expressed cre recombinase transgene resulted in deletion of the miR-10a genomic sequence and its replacement by a residual loxP site, yielding mice with the miR-10a +/- genotype. Mice carrying the miR-10a floxed allele (miR-10a +/-) were intercrossed with C57BL/6 mice for at least 7 generations before generating experimental cohorts. |
| Phenotypic information | Homozygous:To extensively study miR-10a loss we generated a miR-10a knock out mouse. We showed that, in the Apc(min) mouse model of intestinal neoplasia, female miR-10a deficient mice develop significantly more adenomas than miR-10(+/+) and male controls. We further found that lactoperoxidase (Lpo) is extensively upregulated in the intestinal epithelium of mice deprived of miR-10a. Using in vitro assays, we demonstrate that the primary miR-10a target Kruppel-like factor 4 (Klf4) can upregulate transcription of Lpo, whereas siRNA knockdown of Klf4 reduces Lpo levels in HCT-116 cells. Furthermore, Klf4 is upregulated in the intestines of miR-10a knockout mice. Lpo has previously been shown to have the capacity to oxidize estrogens into potent depurinating mutagens, creating an unstable genomic environment that can cause initiation of cancer. Therefore, we postulate that Lpo upregulation in the intestinal epithelium of miR-10a deficient mice together with the predominant abundance of estrogens in female animals mainly accounts for the sex-related cancer phenotype we observed. This suggests that miR-10a could be used as a potent diagnostic marker for discovering groups of women that are at high risk of developing colorectal carcinoma, which today is one of the leading causes of cancer-related deaths.Heterozygous:Not investigated |
| Breeding history | In parallel with intercross breedings of miR-10a +/- males to miR-10a +/- females to generate experimental cohorts, some miR-10a +/- males were backcrossed to C57BL/6 females to maintain the C57BL/6 purity of the strain (N=15). |
| References |
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| Homozygous fertile | not known |
| Homozygous viable | yes |
| Homozygous matings required | no |
| Immunocompromised | no |
Information from EMMA
| Archiving centre | Karolinska Institutet, Stockholm, Sweden |
| Animals used for archiving | heterozygous 0, wild-type 0 |
| Stage of embryos | 2-cell |
Disease and phenotype information
Literature references
- Loss of miR-10a activates lpo and collaborates with activated Wnt signaling in inducing intestinal neoplasia in female mice.;Stadthagen Gustavo, Tehler Disa, Høyland-Kroghsbo Nina Molin, Wen Jiayu, Krogh Anders, Jensen Klaus T, Santoni-Rugiu Eric, Engelholm Lars H, Lund Anders H, ;2013;PLoS genetics;9;e1003913; 24204315