Mouse Genome Informatics
hm1
    Nr2f2tm2.1Tsa/Nr2f2tm2.1Tsa
involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• female homozygotes are subfertile (J:120852)


Mouse Genome Informatics
cn2
    Nr2f2tm2.1Tsa/Nr2f2tm2.1Tsa
involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

cardiovascular system
• thin and well-dilated vessels at E11.5, however did not observe the collapsed or missing anterior cardinal veins displayed by Nr2f2 null mice
• cell layers that separated the artery and vein were greatly reduced at E11.5
• observed budding hematopoietic cell clusters within veins in several regions, including the head vein, the cardinal vein, and the umbilical vein and veins expressed arterial markers Nrp1 (NP-1) and Notch signaling molecules, that were never observed in wildtype veins, suggesting that veins acquire arterial characteristics
• exhibit widespread hemorrhage at E11.5


Mouse Genome Informatics
cn3
    Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+
Nr2f2tm2.1Tsa/Nr2f2tm2.1Tsa
Prox1tm3(cre/ERT2)Gco/Prox1+

involves: 129S1/Sv * 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• embryos exposed to tamoxifen at E10.5-12.5 show some blood-filled dermal lymphatic vessels
• embryos exposed to tamoxifen show reduced number of superficial vessels (X-gal stained); severity of reduction increases with early tamoxifen treatment
• tamoxifen treatment at E10.5 or E11.5 results in severely reduced lymphatic endothelial cell numbers and lack of lymphatic vessels
• embryos exposed to tamoxifen at E10.5 or 11.5 display drastically mispatterned lymph sacs that are reduced in size compared to controls
• when tamoxifen exposure occurs at E13.5, few embryos show any lymphatic defects, while exposure later in development or postnatally causes no obvious defects despite reduction in Nr2f2 expression in LECs

homeostasis/metabolism
• embryos exposed to tamoxifen at E10.5-12.5 (analyzed at E15.5) display edema


Mouse Genome Informatics
cn4
    Gt(ROSA)26Sortm1(CAG-NR2F2)Tsa/Gt(ROSA)26Sor+
Nr2f2tm2.1Tsa/Nr2f2tm2.1Tsa
Pgrtm2(cre)Lyd/Pgr+

involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
N
• uterus defects observed in Nr2f2tm2.1Tsa/Nr2f2tm2.1Tsa Pgr/Pgr+ mice are rescued (J:162256)


Mouse Genome Informatics
cn5
    Nr2f2tm2.1Tsa/Nr2f2tm2.1Tsa
Pgrtm2(cre)Lyd/Pgr+

involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• due to defective embryo attachment and decidualization (J:162256)


Mouse Genome Informatics
cn6
    Nr2f2tm2.1Tsa/Nr2f2tm2.1Tsa
Rbpjtm1Hon/Rbpjtm1Hon
Tg(Tek-cre)1Ywa/0

involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• fewer embryos than expected are found at E10.0

immune system
• at E10.0, number of Prox1+ve lymphatic endothelial cells is dramatically reduced


Mouse Genome Informatics
cn7
    Nr2f2tm2.1Tsa/Nr2f2tm2.1Tsa
Tg(Tek-cre)1Ywa/0

involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• at E10.0, number of Prox1+ve lymphatic endothelial cells is dramatically reduced


Mouse Genome Informatics
cn8
    Amhr2tm3(cre)Bhr/Amhr2+
Nr2f2tm2.1Tsa/Nr2f2tm2.1Tsa

involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• only ~7% of mutant mice are born, indicating embryonic lethality probably due to vascular and heart anomalies resulting from ectopic cre expression

embryogenesis
• by day 10 of pregnancy, formation of fetal blood vessels from the allantois is clearly absent
• at day 9 of pregnancy, but nor earlier, secondary TGC differentiation appears to increase because more cells are present
• by day 10 of pregnancy, many layers of secondary TGC are noted in mutant females relative to control animals
• at day 9 of pregnancy, the mutant uterus displays a reduced number of decidual sites with the absence of embryo or the presence of growth-retarded embryos (J:120852)
• at day 9 of pregnancy, but nor earlier, abnormal placenta development and frequent hemorrhages are observed
• by day 10 of pregnancy, the mutant labyrinth fails to develop
• by day 10 of pregnancy, mutant placentas show a reduction in spongiotrophoblast cell number relative to wild-type placentas
• by day 10 of pregnancy, the mutant labyrinth fails to develop

reproductive system
• at day 9 of pregnancy, the mutant uterus displays a reduced number of decidual sites with the absence of embryo or the presence of growth-retarded embryos (J:120852)
• the circular smooth muscle layer of mutant uteri appears disorganized relative to that of wild-type uteri, as shown by anti-smooth muscle actin immunostaining (J:120852)
• in contrast, the mutant endometrium appears relatively normal (J:120852)
• mutant uterine horns appear shorter than those of control mice (J:120852)
• upon mating with wild-type males, mutant females exhibit a significant lower number of implantation sites per pregnant female than control females (5.3 2.4 vs 8.8 2.2, respectively) (J:120852)
• despite normal ovarian histology and function, mutant female mice receiving a wild-type ovary are unable to produce pups as observed before ovary transfer (J:120852)
• only 1 of 6 mutant females with wild-type ovaries gave birth to one pup in a 6-month period whereas wild-type females carrying mutant ovaries exhibited normal litter sizes with pups derived from the donor ovary (J:120852)
• upon mating with wild-type males, mutant females display vaginal bleeding 10-12 days after the presence of a copulatory plug, indicating failure to maintain pregnancy (J:120852)
• at day 9 of pregnancy, most embryos are reabsorbed and a few are growth-retarded (J:120852)
• however, production of endogenous estradiol and progesterone remains unaffected in mutant females (J:120852)

cardiovascular system
• by day 10 of pregnancy, formation of fetal blood vessels from the allantois is clearly absent
• mutant embryos with hemorrhage are observed

homeostasis/metabolism
• mutant embryos with edema are observed


Mouse Genome Informatics
cn9
    Nr2f2tm2.1Tsa/Nr2f2tm2.1Tsa
Tg(rx3-icre)1Mjam/0

involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
N
• no gross defects in eye development are detected (J:157924)


Mouse Genome Informatics
cn10
    Nr2f1tm2.1Mjts/Nr2f1tm2.1Mjts
Nr2f2tm2.1Tsa/Nr2f2tm2.1Tsa
Tg(rx3-icre)1Mjam/0

involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• not detected at E14.5
• at E11.5 and E14.5 expression analysis indicates that proximo-ventral cells in the presumptive retinal pigment epithelium possess neural retinal identity
• however, nasal-dorsal cells retain their retinal pigment epithelium identity
• at E11.5 expression analysis indicates that progenitor cells in the distal ventral optic stalk gain a neural retinal identity
• at E14.5 a neural retina like structure connects directly with the diencephalon
• at E14.5 expression analysis indicates that proximo-ventral cells in the presumptive retinal pigment epithelium possess neural retinal identity
• at E10.5 the optic stalk resembles the early (E9.5) optic vesicle
• at E12.5 and E14.5 the optic stalk is open ventrally
• the ventral optic stalk is not detected by morphology at E14.5
• however, expression analysis indicates optic stalk identity is maintained but that the boundary between the stalk and neural retina is shifted proximally
• expression analysis indicates that differentiation of dorsal optic stalk cells is impaired
• severe at E14.5
• at E12.5 and E14.5 the optic stalk is open ventrally
• seen at E14.5 and persists through birth

nervous system
• not detected at E14.5

pigmentation
• at E11.5 and E14.5 expression analysis indicates that proximo-ventral cells in the presumptive retinal pigment epithelium possess neural retinal identity
• however, nasal-dorsal cells retain their retinal pigment epithelium identity


Mouse Genome Informatics
cn11
    Nr2f1tm2.1Mjts/Nr2f1+
Nr2f2tm2.1Tsa/Nr2f2tm2.1Tsa
Tg(rx3-icre)1Mjam/0

involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• bilaterally open optic fissure at E14.5


Mouse Genome Informatics
cn12
    Nr2f1tm2.1Mjts/Nr2f1tm2.1Mjts
Nr2f2tm2.1Tsa/Nr2f2+
Tg(rx3-icre)1Mjam/0

involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• bilaterally open optic fissure at E14.5


Mouse Genome Informatics
cn13
    Nkx3-2tm1(cre)Tsa/Nkx3-2+
Nr2f2tm2.1Tsa/Nr2f2tm2.1Tsa

involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
• altered radial patterning and anterior-posterior axis patterning of the stomach
• mesenchyme of the stomach was thickened at E16.5
• hind-stomach was expanded and exhibited a vacuolated epithelium, resembling the pyloric region, with numerous invaginations and a thickened and disorganized circular smooth muscle layer
• the pylorus exhibited a disorganized thickened circular smooth muscle layer, with an epithelium that resembled the epithelium of the duodenum and was devoid of vacuoles, unlike the highly vacuolated control
• number of parietal cells increased in the thickened epithelial layer at E18.5
• thicker epithelium at E12.5, E13.5 and E18.5
• the fore-stomach epithelium did not show signs of stratification at E16.5 and resembled hind-stomach epithelium, indicating posteriorization of stomach
• thicker glandular epithelium at E16.5, however differentiation of this epithelium was unchanged
• exhibited more extensive invagination of the epithelium than in controls
• the circular smooth muscle layer of the stomach was disorganized at E13.5, E14.5 and E15.5 and was thickened in both the fore-stomach and hind-stomach, suggesting that radial patterning of the stomach was perturbed
• slightly smaller stomach at E12.5 than controls
• reduced size of fore-stomach as indicated by an anterior shift of the limited ridge

nervous system
• expansion of enteric neurons in the stomach

muscle
• the circular smooth muscle layer of the stomach was disorganized at E13.5, E14.5 and E15.5 and was thickened in both the fore-stomach and hind-stomach, suggesting that radial patterning of the stomach was perturbed

Mouse Models of Human Disease
OMIM IDRef(s)
Diaphragmatic Hernia, Congenital 142340 J:103437