C57BL/6-Igf2rtm2760.1Arte/H
| Status | Available to order |
| EMMA ID | EM:12712 |
| International strain name | C57BL/6-Igf2rtm2760.1Arte/H |
| Alternative name | C57Bl/6NTac-Igf2rtm2760(I1565A)Arte |
| Strain type | Targeted Mutant Strains : Point mutation |
| Allele/Transgene symbol | Igf2rtm2760.1Arte, |
| Gene/Transgene symbol | Igf2r |
Information from provider
| Provider | Andrew Bassim Hassan |
| Provider affiliation | Sir William Dunn School of Pathology, University of Oxford |
| Genetic information | Knock-in allele into the imprinted Igf2r exon 34 (ATC to GCC) to generate I1565A protein mutation. This disrupts isoleucine in the CD loop of the IGF2 binding domain, that markedly reduces affinity to IGF2. The allele is transmitted through the male germline for breeding (wild-type phenotype) and causes partial lethality and overgrowth when transmitted through the female germline. The allele has been characterised in the following publication: Maternal transmission of an Igf2r domain 11 IGF2 binding mutant allele (Igf2rI1565A) results in partial lethality, overgrowth and intestinal adenoma progression (PMID:31388182). |
| Phenotypic information | Homozygous:Maternal transmission of the homozygous alleles (Igf2rI1565A/I1565A) resulted in normal Mendelian segregation in utero. Embryo growth (wet and dry weight) appeared significantly greater in Igf2rI1565A/I1565A homozygous (118–135%, p=0.0001) mice compared to wild-type littermates. Maternal transmission of the homozygous alleles (Igf2rI1565A/I1565A) resulted in normal Mendelian segregation at birth, but perinatal homozygous Igf2rI1565A/I1565A pups were significantly depleted in number (~20% of expected pups, p=0.0006, X2=14.97) and survival of older pups was significantly worse (log-rank test, p=0.003), with all the pups failing to reach weaning stage.Heterozygous:Maternal transmission of the heterozygous Igf2rI1565A/+p allele resulted in normal Mendelian segregation in utero. Embryo growth (wet and dry weight) appeared significantly greater in Igf2rI1565A/+p heterozygous (114–122%, p less than 0.0001) mice compared to wild-type littermates. Maternal transmission of the Igf2rI1565A/+p heterozygous allele resulted in normal Mendelian segregation at birth, but survival of older pups (neonates) revealed significantly decreased survival (40%) following maternal transmission (log-rank test, p=0.0043). Whole body growth (weight) of the surviving Igf2rI1565A/+p heterozygous pups appeared slightly higher than wild-type littermate controls, with a similar trajectory of growth with time, yet this was not statistically different (p=0.68). Igf2rI1565A/+p heterozygotes exhibited evidence of increased organ growth. Uteri of surviving heterozygous female adult mice appeared grossly enlarged and fluid-filled compared to wild-type littermates, consistent with a degree of vaginal atresia, whereas male genitalia appeared proportionate. We did not observe extra post-axial digits or a kink in the tail of heterozygous mice, phenotypes previously associated with null alleles of Igf2r. Neonatal heart weights were also greater in surviving Igf2rI1565A/+p heterozygotes (p=0.008). Histological examination revealed enlarged hearts with expanded trabecular areas, with extensive regions of haemorrhage in the lungs of Igf2rI1565A/+p heterozygotes compared to wild-type controls. |
| Breeding history | Backcrossed to C57BL/6J for more than 10 generations. |
| References |
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| Homozygous fertile | no |
| Homozygous viable | no |
| Homozygous matings required | no |
| Immunocompromised | no |
Information from EMMA
| Archiving centre | Mary Lyon Centre at MRC Harwell, Oxford, United Kingdom |
Literature references
- Maternal transmission of an Igf2r domain 11: IGF2 binding mutant allele (Igf2rI1565A) results in partial lethality, overgrowth and intestinal adenoma progression.;Hughes Jennifer, Surakhy Mirvat, Can Sermet, Ducker Martin, Davies Nick, Szele Francis, Bühnemann Claudia, Carter Emma, Trikin Roman, Crump Matthew P, Frago Susana, Hassan A Bassim, ;2019;Scientific reports;9;11388; 31388182