Mouse Genome Informatics
hm1
    Krastm1Tyj/Krastm1Tyj
involves: 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• on an inbred genetic background, homozygotes die between E12 and E14
• Background Sensitivity: on a mixed 129S2/SvPas x C57BL/6 genetic background, homozygotes die between E12 and term; the number of viable embryos decreases with increased gestational age, with no mutants surviving past birth

cardiovascular system
• at E12.5, mutant embryos display signs of edema, esp. in the pericardial space

embryogenesis
• homozygotes are morphologically normal up to E10.5, but become readily identifiable by their smaller size at E11.5

growth/size
• homozygotes are morphologically normal up to E10.5, but become readily identifiable by their smaller size at E11.5
• Background Sensitivity: on a mixed 129S2/SvPas x C57BL/6 genetic background, homozygotes show a more severe developmental delay, which is both coordinate and non-coordinate in nature
• Background Sensitivity: at E18.5, some homozygotes of mixed background have developed limbs, skin, tail, and whiskers associated with E17.5-18.5, but eyes associated with E15.5
• beginning at E11.5, mutant embryos of an inbred genetic background exhibit a developmental delay ranging from 0.5 to 3 gestational days
• Background Sensitivity: at E15.5 or older, a small % of homozygotes of mixed background display a non-coordinate development of internal organs

hematopoietic system
• mutant embryos display a perturbed hematopoietic microenvironment in the fetal liver despite normal differentiation of hematopoietic progenitors in vitro or upon transplant into lethally irradiated recipients
• at E12.5, mutant embryos are anemic

homeostasis/metabolism
• at E12.5, mutant embryos display signs of edema, esp. in the pericardial space

liver/biliary system
• at E12.5, mutant livers are significantly smaller than wild-type livers
• at E12.5, mutant livers show a 2- to 8-fold reduction in total cell number relative to wild-type livers
• at E12.5, mutant livers are much paler than wild-type livers

cellular
• at E12.5, mutant fetal livers contain pyknotic nuclei in the distal portion of hepatic lobe
• in severely affected embryos, apoptotic cells are detected throughout the fetal liver

integument
• at E12.5, homozygotes are pale with reduced superficial vasculature


Mouse Genome Informatics
cx2
    Krastm1Tyj/Kras+
Nrastm1Rak/Nrastm1Rak

involves: 129/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• ~30% of these mutants die perinatally
• a few mutant embryos survive up to P2, but are subsequently neglected by their mothers and die shortly thereafter
• ~70% of these mutants die between E10.0 and E12.0

cardiovascular system
• at E10.5, mutant embryos display dilated pericardial sacs
• at E10.5, mutant embryos exhibit a dilated heart

embryogenesis
• at E10.5, mutant embryos exhibit significantly reduced numbers of circulating primitive erythrocytes in either the yolk sac or the embryo
• at E10.5, mutant embryos display a near or complete absence of blood islands in yolk sacs
• at E10.5, mutant yolk sacs appear rough and wrinkled
• at E10.5, mutant embryos appear to have arrested at ~E9.5
• ~30% of abnormal mutant embryos survive beyond this early developmental block but are readily identifiable up until the final stages of gestation
• by E10.5, 65% of viable mutant embryos appear grossly abnormal
• starting at E9.5, ~50% of mutants are delayed by 0.5-1.0 developmental days, but never show the non-coordinate delay observed in late Krastm1Tyj embryos

homeostasis/metabolism
• at E15.5, viable mutant embryos are developmentally delayed and severely edematous

cellular
• at E9.5, mutant embryos display prominent cell death in the forebrain, and to a lesser extent along the neural axis
• by E10.5, cell death extends throughout the entire embryo

hematopoietic system
• at E10.5, mutant embryos exhibit significantly reduced numbers of circulating primitive erythrocytes in either the yolk sac or the embryo
• at E15.5-16.5, mutant fetal livers display a significantly reduced ratio in the number of erythroblasts to hepatocytes
• at E15.5, viable mutant embryos are developmentally delayed and severely anemic
• anemia appears to be attributable to inadequate, but apparently normal, production of definitive erythrocytes and may reflect a defect in the survival or differentiation of either the erythroblasts or a more primitive progenitor cells

vision/eye
• 22% of E13.5-18.5 mutant embryos display an asymmetrical pattern in eye development, involving only the right eye
• either the right eye is significantly smaller than its wild-type counterpart or the pigment of the eye is overgrown

limbs/digits/tail
• 20% of E13.5-18.5 mutant embryos exhibit severe shortening of the tail

liver/biliary system
• by 16.5, a high % of mutant hepatocytes appear extremely vacuolated in the absence of increased cell death

growth/size
• by E10.5, 65% of viable mutant embryos appear grossly abnormal
• starting at E9.5, ~50% of mutants are delayed by 0.5-1.0 developmental days, but never show the non-coordinate delay observed in late Krastm1Tyj embryos

integument
• at E10.5, mutant embryos are significantly paler than wild-type embryos


Mouse Genome Informatics
cx3
    Krastm1Tyj/Krastm1Tyj
Nrastm1Rak/Nrastm1Rak

involves: 129/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• double homozygous mutant blastocyst stage embryos are recovered at approximately the expected frequency of 6%
• no viable double mutant embryos are recovered at E9.5


Mouse Genome Informatics
cx4
    Krastm1Tyj/Krastm1Tyj
Nrastm1Rak/Nras+

involves: 129/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• ~40% of mutant embryos are found dead at E9.5