Mouse Genome Informatics
hm1
    Fggtm1Fjc/Fggtm1Fjc
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• ~25% of newborn homozygotes suffer from primarily abdominal hemorrhages, although hemorrhages around the cranial, neck, and nasal areas are also observed
• however, many homozygotes are able to resolve the bleeding and recover
• ~25% of newborn homozygotes suffer from primarily abdominal hemorrhages
• pregnant female homozygotes consistently present with various degrees of vaginal bleeding beginning at E7 (J:75302)
• excessive maternal bleeding is detected at the implantation site in the uterus as early as E6 (J:75302)

homeostasis/metabolism
• homozygotes exhibit significantly delayed thrombin-induced plasma clot times (>17 min) relative to wild-type mice (35.5 3.5 sec)

reproductive system
• pregnant female homozygotes consistently present with various degrees of vaginal bleeding beginning at E7 (J:75302)
• excessive maternal bleeding is detected at the implantation site in the uterus as early as E6 (J:75302)
• at E6, embryos in the uteri of pregnant female homozygotes show severe bleeding in regions around the ectoplacental cone, resulting in blood-filled lacunae at E8 to E9 (J:75302)
• by E9 large areas of bleeding initiate the disruption of the placenta and yolk sac from the endometrium (J:75302)
• pregnant female homozygotes undergo spontaneous abortion, with resulting maternal death at E9.75 through excessive bleeding (J:75302)
• a minimal dosage schedule of 10 mg of fibrinogen at E8.5 and E17.5 rescues pregnancy and results in successful vaginal deliveries (J:75302)

embryogenesis
• at E9.75, embryos obtained from female pregnant homozygotes are significantly smaller and show bleeding in the egg cylinder cavity
• at E9.75, placental detachment occurs from the implantation site
• female homozygotes exhibit abnormal development of fetal-maternal vascular communication and stabilization of embryo implantation
• afibrinogenemic pregnant females show detachment of the fibrinoid layer from the decidua and disruption of sinusoids of the labyrinths with severe hemorrhage along the planes of placental-decidual attachment
• at E9, embryos obtained from pregnant female homozygotes display a smaller placenta
• at E9.75, embryos obtained from female pregnant homozygotes display a significantly smaller yolk sac

growth/size
• at E9.75, embryos obtained from female pregnant homozygotes are significantly smaller and show bleeding in the egg cylinder cavity

respiratory system
N
• in response to bleomycin-induced acute lung injury, homozygotes show no significant differences in the deposition of interstitial collagen and pulmonary fibrotic lesions at 7 and 14 days after intratracheal administration of bleomycin relative to wild type mice (J:64396)

Mouse Models of Human Disease
OMIM IDRef(s)
Afibrinogenemia, Congenital 202400 J:75302


Mouse Genome Informatics
cx2
    Apobec1tm1Ddsn/Apobec1tm1Ddsn
Fggtm1Fjc/Fggtm1Fjc
Ldlrtm1Her/Ldlrtm1Her

B6.129-Fggtm1Fjc Apobec1tm1Ddsn Ldlrtm1Her
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• display better survival to 3 weeks than do mice only deficient for Fgg

homeostasis/metabolism
• cholesterol is primarily in the LDL fraction as opposed to controls where it is predominantly in the HDL fraction
• thrombin and antithrombin levels very highly elevated

cardiovascular system
• plaque surface area increases beyond what is seen in double homozygotes lacking fibrinogen gamma chain deficiency
• fibrous cap thinner than is seen in double homozygotes lacking fibrinogen gamma chain deficiency
• collagen deposition in plaques develops more rapidly than in double homozygotes lacking fibrinogen gamma chain deficiency