Phenotypes associated with this allele

• Allele Symbol: Kras^tm1Tyj
• Allele Name: targeted mutation 1, Tyler Jacks
• Allele ID: MGI:1857210
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Kras^tm1Tyj/Kras^tm1Tyj	involves: 129S2/SvPas	MGI:3589201
cx2	Kras^tm1Tyj/Kras^+ Nras^tm1Rak/Nras^tm1Rak	involves: 129/Sv * C57BL/6	MGI:3589202
cx3	Kras^tm1Tyj/Kras^tm1Tyj Nras^tm1Rak/Nras^tm1Rak	involves: 129/Sv * C57BL/6	MGI:3589289
cx4	Kras^tm1Tyj/Kras^tm1Tyj Nras^tm1Rak/Nras^+	involves: 129/Sv * C57BL/6	MGI:3589358

Genotype
MGI:3589201

hm1

• Allelic Composition: Kras^tm1Tyj/Kras^tm1Tyj
• Genetic Background: involves: 129S2/SvPas

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

prenatal lethality, complete penetrance ( J:43433 )

• 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

pericardial edema ( J:43433 )

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

embryo

decreased embryo size ( J:43433 )

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

growth/size/body

decreased embryo size ( J:43433 )

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

fetal growth retardation ( J:43433 )

• 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

abnormal definitive hematopoiesis ( J:43433 )

• 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

anemia ( J:43433 )

• at E12.5, mutant embryos are anemic

homeostasis/metabolism

pericardial edema ( J:43433 )

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

liver/biliary system

small liver ( J:43433 )

• at E12.5, mutant livers are significantly smaller than wild-type livers

liver hypoplasia ( J:43433 )

• at E12.5, mutant livers show a 2- to 8-fold reduction in total cell number relative to wild-type livers

pale liver ( J:43433 )

• at E12.5, mutant livers are much paler than wild-type livers

cellular

increased apoptosis ( J:43433 )

• 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

pallor ( J:43433 )

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

Genotype
MGI:3589202

cx2

• Allelic Composition: Kras^tm1Tyj/Kras⁺; Nras^tm1Rak/Nras^tm1Rak
• Genetic Background: involves: 129/Sv * C57BL/6

mortality/aging

postnatal lethality, complete penetrance ( J:43433 )

• a few mutant embryos survive up to P2, but are subsequently neglected by their mothers and die shortly thereafter

perinatal lethality, incomplete penetrance ( J:43433 )

• ~30% of these mutants die perinatally

embryonic lethality during organogenesis, incomplete penetrance ( J:43433 )

• ~70% of these mutants die between E10.0 and E12.0

cardiovascular system

distended pericardium ( J:43433 )

• at E10.5, mutant embryos display dilated pericardial sacs

dilated heart ( J:43433 )

• at E10.5, mutant embryos exhibit a dilated heart

embryo

increased embryonic tissue cell apoptosis ( J:43433 )

• by E10.5, cell death extends throughout the entire embryo

embryonic growth arrest ( J:43433 )

• 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

embryonic growth retardation ( J:43433 )

• 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 Kras^tm1Tyj embryos

absent visceral yolk sac blood islands ( J:43433 )

• at E10.5, mutant embryos display a near or complete absence of blood islands in yolk sacs

excessive folding of visceral yolk sac ( J:43433 )

• at E10.5, mutant yolk sacs appear rough and wrinkled

pale yolk sac ( J:43433 )

abnormal embryonic hematopoiesis ( J:43433 )

• at E10.5, mutant embryos exhibit significantly reduced numbers of circulating primitive erythrocytes in either the yolk sac or the embryo

homeostasis/metabolism

hydrops fetalis ( J:43433 )

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

cellular

increased apoptosis ( J:43433 )

• at E9.5, mutant embryos display prominent cell death in the forebrain, and to a lesser extent along the neural axis

increased embryonic tissue cell apoptosis ( J:43433 )

• by E10.5, cell death extends throughout the entire embryo

hematopoietic system

abnormal embryonic hematopoiesis ( J:43433 )

• at E10.5, mutant embryos exhibit significantly reduced numbers of circulating primitive erythrocytes in either the yolk sac or the embryo

abnormal erythropoiesis ( J:43433 )

• at E15.5-16.5, mutant fetal livers display a significantly reduced ratio in the number of erythroblasts to hepatocytes

anemia ( J:43433 )

• 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

abnormal eye development ( J:43433 )

• 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

short tail ( J:43433 )

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

liver/biliary system

abnormal hepatocyte morphology ( J:43433 )

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

growth/size/body

embryonic growth retardation ( J:43433 )

• 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 Kras^tm1Tyj embryos

integument

pallor ( J:43433 )

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

Genotype
MGI:3589289

cx3

• Allelic Composition: Kras^tm1Tyj/Kras^tm1Tyj; Nras^tm1Rak/Nras^tm1Rak
• Genetic Background: involves: 129/Sv * C57BL/6

mortality/aging

embryonic lethality, complete penetrance ( J:43433 )

• 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

Genotype
MGI:3589358

cx4

• Allelic Composition: Kras^tm1Tyj/Kras^tm1Tyj; Nras^tm1Rak/Nras⁺
• Genetic Background: involves: 129/Sv * C57BL/6

mortality/aging

embryonic lethality, incomplete penetrance ( J:43433 )

• ~40% of mutant embryos are found dead at E9.5