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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Krastm4.1Bbd
targeted mutation 4.1, Mariano Barbacid
MGI:5649285
Summary 4 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Krastm4.1Bbd/Krastm4.1Bbd 129S2.129(Cg)-Krastm4.1Bbd MGI:5649290
hm2
Krastm4.1Bbd/Krastm4.1Bbd B6J.129(FVB)-Krastm4.1Bbd MGI:5649292
hm3
Krastm4.1Bbd/Krastm4.1Bbd involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6J * FVB/N MGI:5649287
ht4
Krastm4.1Bbd/Kras+ involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6J * FVB/N MGI:5649288


Genotype
MGI:5649290
hm1
Allelic
Composition
Krastm4.1Bbd/Krastm4.1Bbd
Genetic
Background
129S2.129(Cg)-Krastm4.1Bbd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Krastm4.1Bbd mutation (0 available); any Kras mutation (56 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• Background Sensitivity: mice exhibit increased, but not complete, perinatal lethality on the 129S2/SvPas background compared to complete lethality on the C57BL/6J background




Genotype
MGI:5649292
hm2
Allelic
Composition
Krastm4.1Bbd/Krastm4.1Bbd
Genetic
Background
B6J.129(FVB)-Krastm4.1Bbd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Krastm4.1Bbd mutation (0 available); any Kras mutation (56 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• Background Sensitivity: complete perinatal lethality on the C57BL/6J background compared to partial perinatal lethality on the 129S2/SvPas background




Genotype
MGI:5649287
hm3
Allelic
Composition
Krastm4.1Bbd/Krastm4.1Bbd
Genetic
Background
involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6J * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Krastm4.1Bbd mutation (0 available); any Kras mutation (56 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• reduced lifespan, with an average half-life of 36 weeks
• perinatal lethality in some mutants, probably due to heart insufficiency and hematopoietic defects
• pregnant females treated with the MEK inhibitor PD0325901 from E7.5 to P9 and then direct treatment of mutant pups until P21 completely rescues perinatal lethality and heart defects observed in P0 pups, as well as the craniofacial dysmorphia and growth defects, however beginning MEK inhibitor treatment at P21 does not ameliorate the developmental defects
• median survival of mutants treated with the MEK inhibitor PD0325901 is 30% longer than vehicle treated mutants

growth/size/body
• cardiac hyperplasia is already evident at E13.5
• increase in heart/body weight ratio characterizes the cardiac hyperplasia at 4 months of age
• facial dysmorphia
• pronounced triangular facial appearance with a shorter distance between the ears and the nose, blunter snout, and wider separation between the eyes
• blunter snout
• shorter distance between the ears and the nose
• surviving mice are smaller at weaning but have normal weight at birth
• surviving mice are smaller at weaning but have normal weight at birth
• at 4 weeks of age, males weigh only 72% of wild-type mice, however this difference is ameliorated by 3 months of age
• at 4 weeks of age, males are 23% shorter than wild-type mice, however this difference is ameliorated by 3 months of age
• severe splenomegaly at 4 months of age

craniofacial
• increase in skull width and height along with reduction in length results in a rounder skull with bigger volume
• at 4 months of age
• at 4 months of age
• at 4 months of age
• facial dysmorphia
• pronounced triangular facial appearance with a shorter distance between the ears and the nose, blunter snout, and wider separation between the eyes
• blunter snout
• shorter distance between the ears and the nose

hearing/vestibular/ear
• shorter distance between the ears and the nose

hematopoietic system
• mice develop a myeloproliferative disorder and exhibit lymphoid and myeloid infiltrates in a variety of organs, including liver, kidney, and lung
• treatment with the MEK inhibitor PD0325901 slows down progression but does not prevent myeloproliferative disease
• splenomegaly is due to congestion and increased extramedullary hematopoiesis
• severe splenomegaly at 4 months of age
• increase in numbers of common myeloid progenitors (Lin-/IL7Ralpha-/Sca-1-/c-Kit+/FcgammaRlow/CD34+)
• splenomegaly is due to congestion and increased extramedullary hematopoiesis
• increase in numbers of granulocyte-macrophage progenitors (Lin-/IL7Ralpha-/Sca-1-/c-Kit+/FcgammaRhigh/CD34+)
• however, numbers of megakaryocyte-erythroid progenitors seem normal
• slight increase in numbers of common lymphoid progenitors (Lin-/IL7Ralpha+/Sca-1low/c-Kitlow)
• decrease in the percentage of CD8+ T cells
• increase in the number of leukocytes in peripheral blood , mainly due to expansion of neutrophils, eosinophils, and basophils
• expansion of myeloid cells in the spleen, with increased levels of both Gr1+/CD11b+ and CD11b+ cells
• mice exhibit an increase in LSK (Lin-/Sca-1+/c-Kit+) cells in the bone marrow
• bone marrow cells proliferate in the absence of cytokines unlike wild-type cells and proliferate more robustly than control bone marrow cells in the presence of cytokines

cardiovascular system
• splenomegaly is due to congestion and increased extramedullary hematopoiesis
• thickening of all chambers
• expansion of Sca-1+/PDGFRalpha+/CD31- cardiac stem cells from hearts of unweaned (P10-P14) mice
• however, mice do not display hypertension, heart fibrosis or cardiovascular remodeling
• increased size of heart is due to an increase in numbers of cardiomyocytes and not by increased cell size
• cardiac hyperplasia is already evident at E13.5
• increase in heart/body weight ratio characterizes the cardiac hyperplasia at 4 months of age
• cardiac output is increased in 4 month old mice
• fractional shortening is increased in 4 month old mice
• 4 month old mice show increased wall thickness in systole, systolic wall thickening, and left ventricle mass, and increased end diastolic volume, however end systolic volume is normal and no differences in the wall thickness in diastole, ejection fraction, or heart rate indicating normal heart function
• higher proliferation rate in cardiomyocytes of 4 month old mice

cellular
• mice that die at P0 show focal necrosis in tissues ilike the liver and muscle
• MEFs show higher growth rate than wild-type MEFs when grown in culture

immune system
• splenomegaly is due to congestion and increased extramedullary hematopoiesis
• severe splenomegaly at 4 months of age
• decrease in the percentage of CD8+ T cells
• increase in the number of leukocytes in peripheral blood , mainly due to expansion of neutrophils, eosinophils, and basophils

muscle
• increased size of heart is due to an increase in numbers of cardiomyocytes and not by increased cell size
• fractional shortening is increased in 4 month old mice
• 4 month old mice show increased wall thickness in systole, systolic wall thickening, and left ventricle mass, and increased end diastolic volume, however end systolic volume is normal and no differences in the wall thickness in diastole, ejection fraction, or heart rate indicating normal heart function

renal/urinary system
• kidneys frequently show infiltration from hematopoietic cells
• however, no abnormalities are seen in renal morphology or histology

skeleton
• increase in skull width and height along with reduction in length results in a rounder skull with bigger volume
• at 4 months of age
• at 4 months of age
• at 4 months of age

vision/eye
• wider separation between the eyes

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Noonan syndrome 3 DOID:0060581 OMIM:609942
J:223433




Genotype
MGI:5649288
ht4
Allelic
Composition
Krastm4.1Bbd/Kras+
Genetic
Background
involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6J * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Krastm4.1Bbd mutation (0 available); any Kras mutation (56 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body

mortality/aging
• mice exhibit a reduced life span, with an average half-life of 62 weeks

hematopoietic system

immune system





Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
08/03/2022
MGI 6.21
The Jackson Laboratory