Phenotypes associated with this allele

• Allele Symbol: Bmpr2^tm1Kmi
• Allele Name: targeted mutation 1, Kohei Miyazono
• Allele ID: MGI:2158503
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Bmpr2^tm1Kmi/Bmpr2^tm1Kmi	involves: 129S4/SvJae * C57BL/6J	MGI:3620990
ht2	Bmpr2^tm1Kmi/Bmpr2^+	involves: 129S4/SvJae	MGI:3526244
ht3	Bmpr2^tm1Kmi/Bmpr2^+	involves: 129S4/SvJae * C57BL/6	MGI:5430760
ht4	Bmpr2^tm1Kmi/Bmpr2^+	involves: 129S4/SvJae * C57BL/6J	MGI:5438770
cn5	Bmpr2^tm1.1Enl/Bmpr2^tm1Kmi Tg(KRT14-cre)1Ipc/0	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:6258665
cx6	Bmpr2^tm1Kmi/Bmpr2^+ Btg2^tm1Spo/Btg2^tm1Spo	involves: 129S4/SvJae * C57BL/6	MGI:3526247
cx7	Bmpr2^tm1Kmi/Bmpr2^+ Ark2c^Gt(P9-3F)Sor/Ark2c^+ Tg(Hlxb9-GFP)1Tmj/0	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:5516589

Genotype
MGI:3620990

hm1

• Allelic Composition: Bmpr2^tm1Kmi/Bmpr2^tm1Kmi
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:61931 )

• at E6.5-E8.5, homozygotes are recovered at the expected Mendelian frequency but appear abnormal

• no homozygotes are recovered at E9.5

embryo

failure to gastrulate ( J:61931 )

• homozygotes fail to undergo normal gastrulation

abnormal rostral-caudal axis patterning ( J:61931 )

• at E7.5, homozygotes lack a properly established A-P axis

embryonic growth arrest ( J:61931 )

• homozygotes are arrested at the egg cylinder stage before gastrulation

embryonic growth retardation ( J:61931 )

• at E6.5, homozygotes exhibit progressive growth retardation and are significantly smaller than wild-type embryos

abnormal embryonic epiblast morphology ( J:61931 )

• at E6.5 and E7.5, homozygotes display impaired epiblast differentiation; in contrast, expression of tissue-specific genes for visceral endoderm differentiation is relatively normal

decreased egg cylinder size ( J:61931 )

• at E6.5, homozygotes fail to form elongated egg cylinders

absent mesoderm ( J:61931 )

• at E7.5, homozygous mutant embryos lack a mesoderm layer

failure of primitive streak formation ( J:61931 )

• at E7.5, homozygotes lack a morphologically identifiable primitive streak

disorganized embryonic tissue ( J:61931 )

abnormal embryonic-extraembryonic boundary morphology ( J:61931 )

• at E6.5, homozygous mutant embryos are disorganized and lack a clear distinction between the embryonic and extraembryonic portions

disorganized extraembryonic tissue ( J:61931 )

growth/size/body

embryonic growth retardation ( J:61931 )

• at E6.5, homozygotes exhibit progressive growth retardation and are significantly smaller than wild-type embryos

Genotype
MGI:3526244

ht2

• Allelic Composition: Bmpr2^tm1Kmi/Bmpr2⁺
• Genetic Background: involves: 129S4/SvJae

skeleton

abnormal sternocostal joint morphology ( J:95124 )

• eight ribs, instead of nine, were attached to the sternum

vertebral transformation ( J:95124 )

• exhibited alleviated vertebral defects compared to homozygous Acvr2b mutants

• transformation of the 23rd vertebra to the 16th thoracic vertebra (as seen in homozygous Acvr2b mutants) was incomplete

• vertebra 29 of most mutants was transformed to the first sacral vertebra instead to the 6th lumbar vertebra (as seen in homozygous Acvr2b mutants)

Genotype
MGI:5430760

ht3

• Allelic Composition: Bmpr2^tm1Kmi/Bmpr2⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

cardiovascular system

abnormal pulmonary artery morphology ( J:98219 )

• heterozygotes exhibit an increase in wall thickness of muscularized pulmonary arteries

• heterozygotes exposed to hypoxia exhibit impaired muscularization of small pulmonary arteries in both the distal intra-acinar vessels and in proximal preacinar vessels, with 25% less increase in wall thickness compared to controls

abnormal lung vasculature morphology ( J:98219 )

• the number of alveoli (and associated capillaries called alveolar-capillary units) per millimeter squared is 40% greater in heterozygotes

• heterozygotes exposed to prolonged hypoxia exhibit impaired pulmonary vascular remodeling, with a smaller increase in pulmonary artery pressure, greater right ventricular hypertrophy, decrease in the number of alveolar-capillary units per millimeter squared, and decreased wall thickness (muscularization) of small pulmonary arteries compared to controls

increased pulmonary vascular resistance ( J:98219 )

• increase in mean total pulmonary vascular resistance and in incremental pulmonary resistance

• however total systemic vascular resistance is not different

increased pulmonary artery pressure ( J:98219 )

• increase in mean pulmonary arterial pressure

• however, mean systemic arterial pressure is not different from controls

• heterozygotes exposed to prolonged hypoxia show a smaller increase in pulmonary artery pressure than control mice

pulmonary hypertension ( J:98219 )

• mutants develop mild pulmonary hypertension

respiratory system

abnormal lung vasculature morphology ( J:98219 )

• the number of alveoli (and associated capillaries called alveolar-capillary units) per millimeter squared is 40% greater in heterozygotes

• heterozygotes exposed to prolonged hypoxia exhibit impaired pulmonary vascular remodeling, with a smaller increase in pulmonary artery pressure, greater right ventricular hypertrophy, decrease in the number of alveolar-capillary units per millimeter squared, and decreased wall thickness (muscularization) of small pulmonary arteries compared to controls

abnormal pulmonary alveolus morphology ( J:98219 )

• the number of alveoli (and associated capillaries called alveolar-capillary units) per millimeter squared is 40% greater in heterozygotes, decreasing the vessels-to-alveoli ratio

Genotype
MGI:5438770

ht4

• Allelic Composition: Bmpr2^tm1Kmi/Bmpr2⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

cardiovascular system

abnormal lung vasculature morphology ( J:117167 )

• mutants with adenovirus-mediated pulmonary overexpression of 5-lipoxygenase to induce inflammation in the lungs exhibit a greater number of muscularized vessels than in the lungs from wild-type mice

pulmonary hypertension ( J:117167 )

• mutants with adenovirus-mediated pulmonary overexpression of 5-lipoxygenase to induce inflammation in the lungs exhibit increased right ventricular systolic pressure compared to wild-type mice with the same treatment, indicating increased sensitivity to stress-induced pulmonary hypertension

• however, mutants exhibit normal right ventricular systolic pressure and do not develop pulmonary hypertension spontaneously under unstressed conditions

increased vasoconstriction ( J:117167 )

• mutants with adenovirus-mediated pulmonary overexpression of 5-lipoxygenase to induce inflammation in the lungs exhibit enhanced pulmonary vasoconstriction

immune system

abnormal leukocyte physiology ( J:117167 )

• minor increase in adhesion of leukocytes to the vessel wall in the lungs

mortality/aging

perinatal lethality, incomplete penetrance ( J:117167 )

• about 20% fewer than the expected number of heterozygous mice were detected, indicating loss in early development

• most mice that do not survive, die in utero, although some die in the immediate postnatal stage

prenatal lethality, incomplete penetrance ( J:117167 )

muscle

increased vasoconstriction ( J:117167 )

• mutants with adenovirus-mediated pulmonary overexpression of 5-lipoxygenase to induce inflammation in the lungs exhibit enhanced pulmonary vasoconstriction

respiratory system

abnormal lung vasculature morphology ( J:117167 )

• mutants with adenovirus-mediated pulmonary overexpression of 5-lipoxygenase to induce inflammation in the lungs exhibit a greater number of muscularized vessels than in the lungs from wild-type mice

hematopoietic system

abnormal leukocyte physiology ( J:117167 )

• minor increase in adhesion of leukocytes to the vessel wall in the lungs

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
primary pulmonary hypertension		DOID:14557	OMIM:178600 OMIM:265400 OMIM:615342 OMIM:615343 OMIM:615344	J:117167

Genotype
MGI:6258665

cn5

• Allelic Composition: Bmpr2^tm1.1Enl/Bmpr2^tm1Kmi; Tg(KRT14-cre)1Ipc/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * SJL

normal phenotype

no abnormal phenotype detected ( J:189569 )

• mice are healthy, fertile, and overtly normal with no apparent skin defects

Genotype
MGI:3526247

cx6

• Allelic Composition: Bmpr2^tm1Kmi/Bmpr2⁺; Btg2^tm1Spo/Btg2^tm1Spo
• Genetic Background: involves: 129S4/SvJae * C57BL/6

skeleton

vertebral transformation ( J:95124 )

• mutants exhibited similar vertebral abnormalities as single homozygous Btg2 mutants, with no differences in the severity of phenotype

Genotype
MGI:5516589

cx7

• Allelic Composition: Bmpr2^tm1Kmi/Bmpr2⁺; Ark2c^Gt(P9-3F)Sor/Ark2c⁺; Tg(Hlxb9-GFP)1Tmj/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

mortality/aging

prenatal lethality, incomplete penetrance ( J:198828 )

• fewer than expected mice are born

• however, all born mice survive to adulthood

nervous system

abnormal motor neuron innervation pattern ( J:198828 )

• some mice exhibit innervation defects in the dorsal forelimb

behavior/neurological

decreased grip strength ( J:198828 )

• some mice exhibit reduced hang time from a cage lid compared with wild-type mice