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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID 		Krit1tm1Kwhi
targeted mutation 1, Kevin Whitehead
MGI:5532525
Summary 9 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
 		Krit1tm1Kwhi/Krit1tm1Kwhi
Nfatc1tm1.1(cre)Bz/Nfatc1+ 		involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6NCrl MGI:6279286
cn2
 		Krit1tm1Kwhi/Krit1tm1Kwhi
Map3k3tm1.1Mlkn/Map3k3+
Nfatc1tm1.1(cre)Bz/Nfatc1+ 		involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6NCrl * C57BL/6NTac MGI:6279292
cn3
 		Krit1tm1Kwhi/Krit1tm1.1Kwhi
Tg(Pdgfb-icre/ERT2,-EGFP)1Frut/0 		involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NCrl * CBA MGI:5661916
cn4
 		Krit1tm1Kwhi/Krit1tm1.1Kwhi
Tg(Tek-cre)1Ywa/0 		involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NCrl * SJL MGI:5661914
cn5
 		Klf2tm1Mlkn/Klf2+
Krit1tm1Kwhi/Krit1tm1Kwhi
Tg(Cdh5-cre/ERT2)1Rha/0 		involves: 129S6/SvEvTac * C57BL/6NCrl MGI:6279216
cn6
 		Klf2tm1Mlkn/Klf2tm1Mlkn
Krit1tm1Kwhi/Krit1tm1Kwhi
Tg(Cdh5-cre/ERT2)1Rha/0 		involves: 129S6/SvEvTac * C57BL/6NCrl MGI:6279217
cn7
 		Klf4tm1Khk/Klf4+
Krit1tm1Kwhi/Krit1tm1Kwhi
Tg(Cdh5-cre/ERT2)1Rha/0 		involves: 129S6/SvEvTac * C57BL/6NCrl MGI:6279218
cn8
 		Krit1tm1Kwhi/Krit1tm1Kwhi
Tg(Cdh5-cre/ERT2)1Rha/0 		involves: 129S6/SvEvTac * C57BL/6NCrl MGI:6279211
cn9
 		Krit1tm1Kwhi/Krit1tm1Kwhi
Map3k3tm1.1Mlkn/Map3k3+
Tg(Cdh5-cre/ERT2)1Rha/0 		involves: 129S6/SvEvTac * C57BL/6NCrl * C57BL/6NTac MGI:6279215


Genotype
MGI:6279286
cn1
Allelic
Composition		 Krit1tm1Kwhi/Krit1tm1Kwhi
Nfatc1tm1.1(cre)Bz/Nfatc1+
Genetic
Background		 involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6NCrl
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Krit1tm1Kwhi mutation (0 available); any Krit1 mutation (35 available)
Nfatc1tm1.1(cre)Bz mutation (0 available); any Nfatc1 mutation (49 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
mortality/aging
lethality throughout fetal growth and development, complete penetrance ( J:238897 )
• mice die prior to birth, with all embryos dead by E14.5-E15.5

cardiovascular system
abnormal heart morphology ( J:238897 )
• hearts show a reduction in space between the endocardium and myocardium that is occupied by cardiac jelly at E10.5 and E12.5
• in the myocardial trabeculae, the myocardium is wrapped tightly by endocardium unlike in wild-type mice where it is separated from the endocardium, indicating loss of endocardial-myocardial separation
abnormal myocardial trabeculae morphology ( J:238897 )
• E10.5 hearts exhibit smaller myocardial trabeculae
thin myocardium ( J:238897 )
• myocardium is thin at E10.5
decreased cardiac jelly amount ( J:238897 )
• area occupied by cardiac jelly in the trabeculae is decreased more than 65% at E10.5
• loss of matrix glycosaminoglycans in the heart, particularly surrounding the trabeculae at E10.5 and loss of intact versican indicates a reduction in cardiac jelly
dilated heart atrium ( J:238897 )
• atrial dilatation is seen at E12.5
dilated heart ventricle ( J:238897 )
• ventricular chamber dilatation is seen at E12.5

muscle
abnormal myocardial trabeculae morphology ( J:238897 )
• E10.5 hearts exhibit smaller myocardial trabeculae
thin myocardium ( J:238897 )
• myocardium is thin at E10.5




Genotype
MGI:6279292
cn2
Allelic
Composition		 Krit1tm1Kwhi/Krit1tm1Kwhi
Map3k3tm1.1Mlkn/Map3k3+
Nfatc1tm1.1(cre)Bz/Nfatc1+
Genetic
Background		 involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6NCrl * C57BL/6NTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Krit1tm1Kwhi mutation (0 available); any Krit1 mutation (35 available)
Map3k3tm1.1Mlkn mutation (0 available); any Map3k3 mutation (27 available)
Nfatc1tm1.1(cre)Bz mutation (0 available); any Nfatc1 mutation (49 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
cardiovascular system
decreased cardiac jelly amount ( J:238897 )
• area occupied by cardiac jelly in the trabeculae is decreased only 25% at E10.5, indicating some rescue of cardiac jelly




Genotype
MGI:5661916
cn3
Allelic
Composition		 Krit1tm1Kwhi/Krit1tm1.1Kwhi
Tg(Pdgfb-icre/ERT2,-EGFP)1Frut/0
Genetic
Background		 involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NCrl * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Krit1tm1.1Kwhi mutation (0 available); any Krit1 mutation (35 available)
Krit1tm1Kwhi mutation (0 available); any Krit1 mutation (35 available)
Tg(Pdgfb-icre/ERT2,-EGFP)1Frut mutation (0 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
cardiovascular system
abnormal brain vasculature morphology ( J:215458 )
• all mice treated with tamoxifen at birth form cerebral cavernous malformations in the brain by 2 months which progress in severity over time
• the lesions in mice treated with tamoxifen at birth show dilated, thin-walled caverns surrounded by hemosiderin deposits, inflammation, and fibrosis
abnormal retina vasculature morphology ( J:215458 )
• mice treated with tamoxifen at birth first show vessel dilation and failure of plexus coalescence in the vascular network at P7, and over time the vascular dilations resolve into caverns and appear as mature retinal cerebral cavernous malformation by P21
• cerebral cavernous malformation lesions in tamoxifen treated mice arise from the superficial vascular plexus and remain superficial until later in disease progression
• mice treated with tamoxifen at P7 develop lesions in the periphery of the retina by P21; these lesions show a similar morphology as those from mice treated with tamoxifen at birth, however severity and size are smaller
• mice treated with tamoxifen at P21 do not develop retinal lesions
abnormal blood vessel physiology ( J:215458 )
• mice treated with tamoxifen at birth exhibit vascular leak in the brain
abnormal vascular endothelial cell physiology ( J:215458 )
• mice treated with tamoxifen at P1 exhibit retinal endothelial hypersprouting
telangiectasia ( J:215458 )
• mice treated with tamoxifen at birth develop simple, dilated telangiectasias that progress to large multi-chambered caverns over time

mortality/aging
premature death ( J:215458 )
• presence of lesions in mice treated with tamoxifen at birth decrease the survival rate

muscle
telangiectasia ( J:215458 )
• mice treated with tamoxifen at birth develop simple, dilated telangiectasias that progress to large multi-chambered caverns over time

nervous system
abnormal brain vasculature morphology ( J:215458 )
• all mice treated with tamoxifen at birth form cerebral cavernous malformations in the brain by 2 months which progress in severity over time
• the lesions in mice treated with tamoxifen at birth show dilated, thin-walled caverns surrounded by hemosiderin deposits, inflammation, and fibrosis

neoplasm
increased retina hemangioma incidence ( J:215458 )
• mice treated with tamoxifen at birth develop mature cerebral cavernous malformation in the retina that recapitulate retinal angiomas by P21

vision/eye
abnormal retina vasculature morphology ( J:215458 )
• mice treated with tamoxifen at birth first show vessel dilation and failure of plexus coalescence in the vascular network at P7, and over time the vascular dilations resolve into caverns and appear as mature retinal cerebral cavernous malformation by P21
• cerebral cavernous malformation lesions in tamoxifen treated mice arise from the superficial vascular plexus and remain superficial until later in disease progression
• mice treated with tamoxifen at P7 develop lesions in the periphery of the retina by P21; these lesions show a similar morphology as those from mice treated with tamoxifen at birth, however severity and size are smaller
• mice treated with tamoxifen at P21 do not develop retinal lesions
increased retina hemangioma incidence ( J:215458 )
• mice treated with tamoxifen at birth develop mature cerebral cavernous malformation in the retina that recapitulate retinal angiomas by P21
eye lesions ( J:215458 )
• cavernous malformation lesions form in the retinas of mice treated with tamoxifen at birth
• retinal lesions in mice treated with tamoxifen at birth arise in the veins located both most superior and inferior within the retina




Genotype
MGI:5661914
cn4
Allelic
Composition		 Krit1tm1Kwhi/Krit1tm1.1Kwhi
Tg(Tek-cre)1Ywa/0
Genetic
Background		 involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NCrl * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Krit1tm1.1Kwhi mutation (0 available); any Krit1 mutation (35 available)
Krit1tm1Kwhi mutation (0 available); any Krit1 mutation (35 available)
Tg(Tek-cre)1Ywa mutation (6 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
mortality/aging
embryonic lethality during organogenesis, complete penetrance ( J:215458 )
• embryos do not survive beyond E12.5 due to failed vascular development

cardiovascular system
abnormal vascular development ( J:215458 )
• embryos exhibit failed vascular development
abnormal pharyngeal arch artery morphology ( J:215458 )
• branchial arch arteries fail to lumenize properly
abnormal blood circulation ( J:215458 )
• failure of proper embryonic circulation due to disrupted vessel formation

embryo
abnormal pharyngeal arch artery morphology ( J:215458 )
• branchial arch arteries fail to lumenize properly

craniofacial
abnormal pharyngeal arch artery morphology ( J:215458 )
• branchial arch arteries fail to lumenize properly




Genotype
MGI:6279216
cn5
Allelic
Composition		 Klf2tm1Mlkn/Klf2+
Krit1tm1Kwhi/Krit1tm1Kwhi
Tg(Cdh5-cre/ERT2)1Rha/0
Genetic
Background		 involves: 129S6/SvEvTac * C57BL/6NCrl
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Klf2tm1Mlkn mutation (0 available); any Klf2 mutation (12 available)
Krit1tm1Kwhi mutation (0 available); any Krit1 mutation (35 available)
Tg(Cdh5-cre/ERT2)1Rha mutation (4 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
cardiovascular system
abnormal brain vasculature morphology ( J:232707 )
• tamoxifen injected mice exhibit a marked (80%) but incomplete prevention of cerebral cavernous malformation lesion formation

nervous system
abnormal brain vasculature morphology ( J:232707 )
• tamoxifen injected mice exhibit a marked (80%) but incomplete prevention of cerebral cavernous malformation lesion formation




Genotype
MGI:6279217
cn6
Allelic
Composition		 Klf2tm1Mlkn/Klf2tm1Mlkn
Krit1tm1Kwhi/Krit1tm1Kwhi
Tg(Cdh5-cre/ERT2)1Rha/0
Genetic
Background		 involves: 129S6/SvEvTac * C57BL/6NCrl
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Klf2tm1Mlkn mutation (0 available); any Klf2 mutation (12 available)
Krit1tm1Kwhi mutation (0 available); any Krit1 mutation (35 available)
Tg(Cdh5-cre/ERT2)1Rha mutation (4 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
nervous system
nervous system phenotype ( J:232707 )
N
• mice exhibit 99% rescue of cerebral cavernous malformation lesion formation, with only a small amount of venule dilatation visible




Genotype
MGI:6279218
cn7
Allelic
Composition		 Klf4tm1Khk/Klf4+
Krit1tm1Kwhi/Krit1tm1Kwhi
Tg(Cdh5-cre/ERT2)1Rha/0
Genetic
Background		 involves: 129S6/SvEvTac * C57BL/6NCrl
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Klf4tm1Khk mutation (1 available); any Klf4 mutation (26 available)
Krit1tm1Kwhi mutation (0 available); any Krit1 mutation (35 available)
Tg(Cdh5-cre/ERT2)1Rha mutation (4 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
cardiovascular system
abnormal brain vasculature morphology ( J:232707 )
• tamoxifen injected mice exhibit a marked (75%) but incomplete prevention of cerebral cavernous malformation lesion formation

nervous system
abnormal brain vasculature morphology ( J:232707 )
• tamoxifen injected mice exhibit a marked (75%) but incomplete prevention of cerebral cavernous malformation lesion formation




Genotype
MGI:6279211
cn8
Allelic
Composition		 Krit1tm1Kwhi/Krit1tm1Kwhi
Tg(Cdh5-cre/ERT2)1Rha/0
Genetic
Background		 involves: 129S6/SvEvTac * C57BL/6NCrl
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Krit1tm1Kwhi mutation (0 available); any Krit1 mutation (35 available)
Tg(Cdh5-cre/ERT2)1Rha mutation (4 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
mortality/aging
premature death ( J:232707 )
• almost all tamoxifen injected mice are dead by P30

cardiovascular system
abnormal brain vasculature morphology ( J:232707 , J:250906 )
• vascular malformation are first seen at P6 of tamoxifen injected mice as dilated venules in the cerebellar white matter, with numerous mature lesions present by P11 (J:232707)
• mice injected with tamoxifen at P1 exhibit cerebral cavernous malformation lesions by P13 (J:250906)
abnormal venule morphology ( J:232707 )
• tamoxifen injected mice exhibit dilated venules in the cerebellar white matter

nervous system
abnormal brain vasculature morphology ( J:232707 , J:250906 )
• vascular malformation are first seen at P6 of tamoxifen injected mice as dilated venules in the cerebellar white matter, with numerous mature lesions present by P11 (J:232707)
• mice injected with tamoxifen at P1 exhibit cerebral cavernous malformation lesions by P13 (J:250906)

Mouse Models of Human Disease
 DO ID OMIM ID(s) Ref(s)
cerebral cavernous malformation DOID:0060669 OMIM:PS116860
 J:232707 , J:250906




Genotype
MGI:6279215
cn9
Allelic
Composition		 Krit1tm1Kwhi/Krit1tm1Kwhi
Map3k3tm1.1Mlkn/Map3k3+
Tg(Cdh5-cre/ERT2)1Rha/0
Genetic
Background		 involves: 129S6/SvEvTac * C57BL/6NCrl * C57BL/6NTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Krit1tm1Kwhi mutation (0 available); any Krit1 mutation (35 available)
Map3k3tm1.1Mlkn mutation (0 available); any Map3k3 mutation (27 available)
Tg(Cdh5-cre/ERT2)1Rha mutation (4 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
nervous system
nervous system phenotype ( J:232707 )
N
• tamoxifen injected mice show a reduction in the number and size of vascular lesions in the brain at P11, with nearly complete prevention of lesions




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Send questions and comments to User Support. 		last database update
11/12/2024
MGI 6.24 		The Jackson Laboratory