C57BL/6-Igf2rtm2760.1Arte/H

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EMMA IDEM:12712
Citation informationRRID:IMSR_EM:12712 

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International strain nameC57BL/6-Igf2rtm2760.1Arte/H
Alternative nameC57Bl/6NTac-Igf2rtm2760(I1565A)Arte
Strain typeTargeted Mutant Strains : Point mutation
Allele/Transgene symbolIgf2rtm2760.1Arte
Gene/Transgene symbolIgf2r

Information from provider

ProviderAndrew Bassim Hassan
Provider affiliationSir William Dunn School of Pathology, University of Oxford
Genetic informationKnock-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 informationHomozygous:
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 historyBackcrossed to C57BL/6J for more than 10 generations.
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
Homozygous fertileno
Homozygous viableno
Homozygous matings requiredno
Immunocompromisedno

Information from EMMA

Archiving centreMary Lyon Centre at MRC Harwell, Oxford, United Kingdom

Disease and phenotype information

MGI phenotypes (gene matching)
  • enlarged heart / MGI
  • heart hyperplasia / MGI
  • abnormal interventricular septum morphology / MGI
  • abnormal craniofacial morphology / MGI
  • polydactyly / MGI
  • kinked tail / MGI
  • short tail / MGI
  • enlarged liver / MGI
  • abnormal body water content / MGI
  • abnormal uterus morphology / MGI
  • vagina atresia / MGI
  • abnormal lung morphology / MGI
  • abnormal lung development / MGI
  • increased body weight / MGI
  • increased body size / MGI
  • absent suckling reflex / MGI
  • cyanosis / MGI
  • increased embryo size / MGI
  • edema / MGI
  • reduced male fertility / MGI
  • reduced female fertility / MGI
  • female infertility / MGI
  • decreased litter size / MGI
  • respiratory failure / MGI
  • respiratory distress / MGI
  • abnormal motor capabilities/coordination/movement / MGI
  • abnormal embryonic growth/weight/body size / MGI
  • disorganized myocardium / MGI
  • abnormal tricuspid valve morphology / MGI
  • dilated heart left ventricle / MGI
  • dilated heart right ventricle / MGI
  • increased heart weight / MGI
  • thick ventricular wall / MGI
  • enlarged kidney / MGI
  • genetic imprinting / MGI
  • maternal imprinting / MGI
  • abnormal external female genitalia morphology / MGI
  • abnormal lysosome physiology / MGI
  • premature bone ossification / MGI
  • increased fetal size / MGI
  • pulmonary hyperplasia / MGI
  • enlarged placenta / MGI
  • split sternum / MGI
  • short sternum / MGI
  • enlarged lung / MGI
  • enlarged uterus / MGI
  • increased placenta weight / MGI
  • dilated heart / MGI
  • liver hyperplasia / MGI
  • increased brain size / MGI
  • abnormal myocardium layer morphology / MGI
  • homeostasis/metabolism phenotype / MGI
  • growth/size/body region phenotype / MGI
  • reproductive system phenotype / MGI
  • abnormal circulating hormone level / MGI
  • congestive heart failure / MGI
  • thin endometrium / MGI
  • abnormal bone ossification / MGI
  • decreased survivor rate / MGI
  • increased heart ventricle size / MGI
  • abnormal uterine horn morphology / MGI
  • dilated uterine horn / MGI
  • absent endometrial glands / MGI
  • increased nucleated erythrocyte cell number / MGI
  • decreased fetal weight / MGI
  • increased fetal weight / MGI
  • increased birth weight / MGI
  • heart hemorrhage / MGI
  • increased birth body size / MGI
  • increased heart right ventricle size / MGI
  • thick interventricular septum / MGI
  • mortality/aging / MGI
  • impaired branching involved in preterminal bronchiole morphogenesis / MGI
  • postnatal lethality, complete penetrance / MGI
  • postnatal lethality, incomplete penetrance / MGI
  • neonatal lethality, complete penetrance / MGI
  • neonatal lethality, incomplete penetrance / MGI
  • perinatal lethality, incomplete penetrance / MGI
  • prenatal lethality, complete penetrance / MGI
  • lethality throughout fetal growth and development, incomplete penetrance / MGI
  • preweaning lethality, incomplete penetrance / MGI
  • enlarged uterine horn / MGI

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

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