Phenotypes associated with this allele

• Allele Symbol: Bmpr1a^tm2.1Bhr
• Allele Name: targeted mutation 2.1, Richard R Behringer
• Allele ID: MGI:2158390
• Summary: 23 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Bax^tm1Sjk/Bax^tm1Sjk Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr Tg(Sftpc-cre)1Blh/0	involves: 129 * C57BL/6 * DBA/2 * ICR	MGI:3811313
cn2	Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.2Bhr Tg(Gdf5-cre,-ALPP)1Kng/0	involves: 129 * C57BL/6 * FVB/N-Tg(Gdf5-cre-ALPP)1Kng	MGI:3578783
cn3	Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Krt14^tm1.1(cre)Wbm/Krt14^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd	MGI:5508225
cn4	Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Ctnnb1^tm1Mmt/Ctnnb1^+ Krt14^tm1.1(cre)Wbm/Krt14^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * 129X1/SvJ	MGI:5508218
cn5	Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Kdr^tm1(cre)Sato/Kdr^+	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:3687380
cn6	Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.2Bhr Isl1^tm1(cre)Sev/Isl1^+	involves: 129S4/SvJae * 129S7/SvEvBrd	MGI:3625139
cn7	Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Tg(Col1a1-cre/Esr1*)1Mis/0	involves: 129S7/SvEvBrd	MGI:3829249
cn8	Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Shh^tm1(EGFP/cre)Cjt/?	involves: 129S7/SvEvBrd	MGI:5305710
cn9	Amhr2^tm3(cre)Bhr/Amhr2^+ Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr	involves: 129S7/SvEvBrd * C57BL/6	MGI:3042225
cn10	Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:4941477
cn11	Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:6404152
cn12	Bmpr1a^tm2.1Bhr/Bmpr1a^+ Tg(Sftpc-cre)1Blh/0	involves: 129S7/SvEvBrd * C57BL/6 * DBA/2	MGI:3811322
cn13	Bmpr1a^tm2.1Bhr/Bmpr1a^+ Tg(Sftpc-cre)1Blh/0	involves: 129S7/SvEvBrd * C57BL/6 * DBA/2 * ICR	MGI:3811314
cn14	Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr Tg(Sftpc-cre)1Blh/0	involves: 129S7/SvEvBrd * C57BL/6 * DBA/2 * ICR	MGI:3811312
cn15	Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr Tg(GATA6-cre)#Jbeb/0	involves: 129S7/SvEvBrd * C57BL/6 * FVB	MGI:3663711
cn16	Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr Tg(Cga-cre)3Sac/0	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3819176
cn17	Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Tg(Col2a1-cre)1Bhr/?	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3785772
cn18	Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr Tg(Pou3f4-cre)32Cren/0	involves: 129S7/SvEvBrd * CD-1	MGI:2181350
cn19	Bmpr1a^tm2.1Bhr/Bmpr1a^+ Tg(Pou3f4-cre)32Cren/0	involves: 129S7/SvEvBrd * CD-1	MGI:2181351
cn20	Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr Bmpr1b^tm1Kml/Bmpr1b^tm1Kml Tg(Six3-cre)69Frty/0	involves: 129S/SvEv	MGI:3574977
cn21	Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr Bmpr1b^tm1Kml/Bmpr1b^+ Tg(Six3-cre)69Frty/0	involves: 129S/SvEv	MGI:3574976
cn22	Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Bmpr1b^tm1Kml/Bmpr1b^tm1Kml Tg(Col2a1-cre)1Bhr/?	involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3785771
cn23	Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr Tg(Six3-cre)69Frty/0	Not Specified	MGI:3574975

Genotype
MGI:3811313

cn1

• Allelic Composition: Bax^tm1Sjk/Bax^tm1Sjk; Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr; Tg(Sftpc-cre)1Blh/0
• Genetic Background: involves: 129 * C57BL/6 * DBA/2 * ICR

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

respiratory system

abnormal lung development ( J:106392 )

• while increased apoptosis of epithelial cells is rescued, mice exhibit abnormal branching morphogenesis

Genotype
MGI:3578783

cn2

• Allelic Composition: Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.2Bhr; Tg(Gdf5-cre,-ALPP)1Kng/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/N-Tg(Gdf5-cre-ALPP)1Kng

Joint defects in Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.2Bhr Tg(Gdf5-cre,-ALPP)1Kng/0 mice

skeleton

osteoarthritis ( J:97780 )

• digit joints are normal at birth but cartilage is lost as the mutants age; however neutrophils are not seen in the joints

• deterioration similar to that in the foot is also seen in the knee

osteosclerosis ( J:97780 )

• at 7 weeks and 9 months, subchondral sclerosis is seen, especially in the epiphysis of the femur

abnormal articular cartilage morphology ( J:97780 )

• many joints, including those in the foot and the knee, showed a decrease in cartilage however cartilage was normal in non-articular regions

• cartilage formation is reduced and cells with a noncartilaginous appearance are seen in the fibrocartilaginous meniscus that sits between the femur and tibia

abnormal synovial joint membrane morphology ( J:97780 )

• hypertrophy of the synovial membrane is seen in some joints, particulary in the ankle region

• in severely affected joints the synovial membrane grows into the joint space and this is associated with articular cartilage loss

• synovial hypertophy decreases with age

fused joints ( J:97780 )

• at some sites in the ankles the joints appear to be absent and bones that are normally separated are fused

• in all mutants the second distal tarsal was fused to the central tarsal bone

abnormal skeleton development ( J:97780 )

• E15.5 expression of early joint markers is decreased in the ankle suggesting the fusion of some of the ankle joints is a result of incomplete segmentation

abnormal long bone epiphysis morphology ( J:97780 )

• at 7 weeks and 9 months, the domed epiphysis of the tibia is flattened and depressed

abnormal cartilage development ( J:97780 )

• accelerated cartilage maturation is seen

decreased joint mobility ( J:97780 )

• the range of motion of the digit joints is reduced

behavior/neurological

decreased grip strength ( J:97780 )

• the ability to grasp and remain suspended from a slender rod is significantly reduced

hearing/vestibular/ear

abnormal ear shape ( J:97780 )

• the ears are shorter and often lay flatter against the head

short ears ( J:97780 )

• the ears are shorter than normal

limbs/digits/tail

syndactyly ( J:97780 )

• soft tissue syndactyly is seen involving the first and second digits that is more severe and more frequent in the forefeet compared to the hindfeet (incidence of 91% and 50%, respectively)

• decreased apoptosis is seen at E14.5 between the first and second digits and in the posterior margin of the fifth digit

immune system

osteoarthritis ( J:97780 )

• digit joints are normal at birth but cartilage is lost as the mutants age; however neutrophils are not seen in the joints

• deterioration similar to that in the foot is also seen in the knee

craniofacial

abnormal ear shape ( J:97780 )

• the ears are shorter and often lay flatter against the head

short ears ( J:97780 )

• the ears are shorter than normal

growth/size/body

abnormal ear shape ( J:97780 )

• the ears are shorter and often lay flatter against the head

short ears ( J:97780 )

• the ears are shorter than normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteoarthritis		DOID:8398		J:97780

Genotype
MGI:5508225

cn3

• Allelic Composition: Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr; Krt14^{tm1.1(cre)Wbm}/Krt14⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd

neoplasm

neoplasm ( J:199091 )

N • mice do not develop salivary gland squamous cell carcinoma

Genotype
MGI:5508218

cn4

• Allelic Composition: Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr; Ctnnb1^tm1Mmt/Ctnnb1⁺; Krt14^{tm1.1(cre)Wbm}/Krt14⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * 129X1/SvJ

mortality/aging

decreased tumor-free survival time ( J:199091 )

• mutants succumb to tumors rapidly, dying between P75 and P90

neoplasm

increased salivary gland tumor incidence ( J:199091 )

• rapidly develop aggressive tumors in the salivary glands

• tumors contain transplantable and hyperproliferative tumor propagating cells (CD24+CD29+)

• treatment of cultured CD24+CD29+ tumor cells with the canonical Wnt inhibitor ICG-001 blocks proliferation of these cells

• CD24+CD29+ tumor propagating cells from salivary gland tumors exhibit unrestricted self-renewal in salisphere culture

increased squamous cell carcinoma incidence ( J:199091 )

• tumors arise from the submandibular salivary glands and are classified as salivary gland squamous cell carcinoma

digestive/alimentary system

increased salivary gland tumor incidence ( J:199091 )

• rapidly develop aggressive tumors in the salivary glands

• tumors contain transplantable and hyperproliferative tumor propagating cells (CD24+CD29+)

• treatment of cultured CD24+CD29+ tumor cells with the canonical Wnt inhibitor ICG-001 blocks proliferation of these cells

• CD24+CD29+ tumor propagating cells from salivary gland tumors exhibit unrestricted self-renewal in salisphere culture

endocrine/exocrine glands

increased salivary gland tumor incidence ( J:199091 )

• rapidly develop aggressive tumors in the salivary glands

• tumors contain transplantable and hyperproliferative tumor propagating cells (CD24+CD29+)

• treatment of cultured CD24+CD29+ tumor cells with the canonical Wnt inhibitor ICG-001 blocks proliferation of these cells

• CD24+CD29+ tumor propagating cells from salivary gland tumors exhibit unrestricted self-renewal in salisphere culture

integument

increased hair follicle number ( J:199091 )

• excessive supernumerary hair follicles in the skin

craniofacial

increased salivary gland tumor incidence ( J:199091 )

• rapidly develop aggressive tumors in the salivary glands

• tumors contain transplantable and hyperproliferative tumor propagating cells (CD24+CD29+)

• treatment of cultured CD24+CD29+ tumor cells with the canonical Wnt inhibitor ICG-001 blocks proliferation of these cells

• CD24+CD29+ tumor propagating cells from salivary gland tumors exhibit unrestricted self-renewal in salisphere culture

growth/size/body

increased salivary gland tumor incidence ( J:199091 )

• rapidly develop aggressive tumors in the salivary glands

• tumors contain transplantable and hyperproliferative tumor propagating cells (CD24+CD29+)

• treatment of cultured CD24+CD29+ tumor cells with the canonical Wnt inhibitor ICG-001 blocks proliferation of these cells

• CD24+CD29+ tumor propagating cells from salivary gland tumors exhibit unrestricted self-renewal in salisphere culture

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
salivary gland carcinoma		DOID:0050904		J:199091

Genotype
MGI:3687380

cn5

• Allelic Composition: Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr; Kdr^tm1(cre)Sato/Kdr⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:112269 )

• die between E10.5 and E11.5

growth/size/body

decreased embryo size ( J:112269 )

embryo

abnormal vitelline vasculature morphology ( J:112269 )

• E10.5 yolk sacs show only the primary vascular plexus of poorly developed vascular channels instead of large vessels with extensive branching and well-developed capillary network

embryonic growth arrest ( J:112269 )

• fail to develop beyond E11.5 as indicated by the small size and failure to form digits at E12.5

decreased embryo size ( J:112269 )

abnormal visceral yolk sac morphology ( J:112269 )

pale yolk sac ( J:112269 )

• 21 of 69 exhibit pale yolk sacs at E10.5 and by E11.5, all mutants have pale yolk sacs

cardiovascular system

abnormal vascular development ( J:112269 )

• exhibit defective vessel development

abnormal vascular branching morphogenesis ( J:112269 )

• often show abnormal branching in the trunk

abnormal vitelline vasculature morphology ( J:112269 )

• E10.5 yolk sacs show only the primary vascular plexus of poorly developed vascular channels instead of large vessels with extensive branching and well-developed capillary network

vascular smooth muscle hypoplasia ( J:112269 )

• exhibit fewer smooth muscle cell numbers around the dorsal aortas and those that are present do not make close contacts with adjacent endothelial cells

abnormal vein morphology ( J:112269 )

• often show dilated vessels in the brain

absent atrioventricular cushions ( J:112269 )

• at E10.5, the atrioventricular canal endocardial cushion is absent, however the development of the outflow tract cushion appears normal

small heart ( J:112269 )

pericardial effusion ( J:112269 )

• cavity between the pericardial sac and the heart is distended

hemorrhage ( J:112269 )

• all mutants exhibit hemorrhage throughout the trunk region of the embryo at E11.5

internal hemorrhage ( J:112269 )

• embryos surviving to E11.5 are morphologically normal at E10.5 but subsequently succumb to death displaying abdominal hemorrhage

muscle

vascular smooth muscle hypoplasia ( J:112269 )

• exhibit fewer smooth muscle cell numbers around the dorsal aortas and those that are present do not make close contacts with adjacent endothelial cells

hematopoietic system

hematopoietic system phenotype ( J:112269 )

N • exhibit normal embryonic and definitive hematopoiesis

homeostasis/metabolism

pericardial effusion ( J:112269 )

• cavity between the pericardial sac and the heart is distended

integument

pallor ( J:112269 )

• at E12.5, embryos are totally pale, although some of them still have red fluid within the amnion

Genotype
MGI:3625139

cn6

• Allelic Composition: Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.2Bhr; Isl1^tm1(cre)Sev/Isl1⁺
• Genetic Background: involves: 129S4/SvJae * 129S7/SvEvBrd

embryo

abnormal hindlimb bud morphology ( J:107396 )

• by E11.5 ectopic outgrowths were observed on the ventral surface of the hindlimb bud

small hindlimb buds ( J:107396 )

• at E10, hindlimb buds were smaller

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:107396 )

• mutants were recovered at mendelian frequencies at E10.5

• began to be lost by E11.5 and no live mutant were recovered at E14.5

cardiovascular system

persistent truncus arteriosus ( J:107396 )

• abnormalities of outflow tract and right ventricle was evident by E8.5

• at E13.5 severe abnormalities of outflow tract formation with evident of persistent truncus arteriosus and underdeveloped valves

abnormal fetal cardiomyocyte proliferation ( J:107396 )

• proliferation of ventricular myocardium in the free wall and septum was also decreased in mutants relative to controls

muscle

abnormal fetal cardiomyocyte proliferation ( J:107396 )

• proliferation of ventricular myocardium in the free wall and septum was also decreased in mutants relative to controls

abnormal cardiomyocyte apoptosis ( J:107396 )

• decreased apoptosis in outflow tract cushions and increased apoptosis atop the ventricular septum

limbs/digits/tail

abnormal hindlimb bud morphology ( J:107396 )

• by E11.5 ectopic outgrowths were observed on the ventral surface of the hindlimb bud

small hindlimb buds ( J:107396 )

• at E10, hindlimb buds were smaller

abnormal hindlimb morphology ( J:107396 )

• by E13.5 hindlimb formation was severely abnormal

cellular

abnormal fetal cardiomyocyte proliferation ( J:107396 )

• proliferation of ventricular myocardium in the free wall and septum was also decreased in mutants relative to controls

abnormal cardiomyocyte apoptosis ( J:107396 )

• decreased apoptosis in outflow tract cushions and increased apoptosis atop the ventricular septum

decreased cell proliferation ( J:107396 )

• proliferation of developing hindlimb buds was severely decreased

Genotype
MGI:3829249

cn7

• Allelic Composition: Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr; Tg(Col1a1-cre/Esr1*)1Mis/0
• Genetic Background: involves: 129S7/SvEvBrd

skeleton

abnormal skeleton morphology ( J:143588 )

enlarged parietal bone ( J:143588 )

• at E18.5, the parietal bone of tamoxifen-treated mice is thicker than in wild-type mice

abnormal bone structure ( J:143588 )

• bony areas of tamoxifen-treated mice are loose, discontinuous and disorganized compared to in wild-type mice

abnormal osteoclast differentiation ( J:143588 )

• as determined by marker expression, tamoxifen-treated mice exhibit reduced osteoclastogenesis compared to wild-type mice

decreased osteoclast cell number ( J:143588 )

• in tamoxifen-treated mice

increased bone mass ( J:143588 )

• at E18.5, tamoxifen-treated mice exhibit a 30% increase in bone volume to total tissue volume in the calvariae and femora compared to wild-type mice

• tamoxifen-treated mice exhibit increased bone mass in femora and calvariae compared to in wild-type mice

abnormal skeleton physiology ( J:143588 )

abnormal osteoclast physiology ( J:143588 )

• tamoxifen-treated mice exhibit reduced osteoclast activity compared to in wild-type mice

increased bone mineralization ( J:143588 )

• bone mineralization of calvariae from mice treated with tamoxifen is increased and bone continuity is disrupted compared to in wild-type mice

decreased bone ossification ( J:143588 )

• as determined by expression of markers, tamoxifen-treated mice exhibit a modest reduction in E16.5 bone formation compared to in wild-type mice

immune system

abnormal osteoclast differentiation ( J:143588 )

• as determined by marker expression, tamoxifen-treated mice exhibit reduced osteoclastogenesis compared to wild-type mice

decreased osteoclast cell number ( J:143588 )

• in tamoxifen-treated mice

abnormal osteoclast physiology ( J:143588 )

• tamoxifen-treated mice exhibit reduced osteoclast activity compared to in wild-type mice

hematopoietic system

abnormal osteoclast differentiation ( J:143588 )

• as determined by marker expression, tamoxifen-treated mice exhibit reduced osteoclastogenesis compared to wild-type mice

decreased osteoclast cell number ( J:143588 )

• in tamoxifen-treated mice

abnormal osteoclast physiology ( J:143588 )

• tamoxifen-treated mice exhibit reduced osteoclast activity compared to in wild-type mice

craniofacial

enlarged parietal bone ( J:143588 )

• at E18.5, the parietal bone of tamoxifen-treated mice is thicker than in wild-type mice

cellular

abnormal osteoclast differentiation ( J:143588 )

• as determined by marker expression, tamoxifen-treated mice exhibit reduced osteoclastogenesis compared to wild-type mice

Genotype
MGI:5305710

cn8

• Allelic Composition: Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr; Shh^{tm1(EGFP/cre)Cjt}/?
• Genetic Background: involves: 129S7/SvEvBrd

mortality/aging

preweaning lethality, complete penetrance ( J:166768 )

• most homozygotes die in utero or at birth

• some survival to 9 days of age

Genotype
MGI:3042225

cn9

• Allelic Composition: Amhr2^tm3(cre)Bhr/Amhr2⁺; Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

reproductive system

male pseudohermaphroditism ( J:89999 )

• in addition to a normal male reproductive tract, XY mice developed uteri and oviducts

secondary sex reversal ( J:89999 )

Genotype
MGI:4941477

cn10

• Allelic Composition: Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

skeleton

skeleton phenotype ( J:169133 )

N • tamoxifen-treated mice exhibit normal sclerotome formation

Genotype
MGI:6404152

cn11

• Allelic Composition: Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

digestive/alimentary system

abnormal gastric gland morphology ( J:163367 )

• antral and pyloric hyperplasia and distended antral-pyloric region in tamoxifen-treated mice

abnormal pyloric gastric gland morphology ( J:163367 )

• hyperplasia in tamoxifen-treated mice

abnormal stomach epithelium morphology ( J:163367 )

• foveolar hyperplasia in tamoxifen-treated mice

gastric polyps ( J:163367 )

• in tamoxifen-treated mice

stomach inflammation ( J:163367 )

• acute and chronic in antral polyps of tamoxifen-treated mice

endocrine/exocrine glands

abnormal gastric gland morphology ( J:163367 )

• antral and pyloric hyperplasia and distended antral-pyloric region in tamoxifen-treated mice

abnormal pyloric gastric gland morphology ( J:163367 )

• hyperplasia in tamoxifen-treated mice

abnormal submucosal gland morphology ( J:163367 )

• hyperplastic in tamoxifen-treated mice

immune system

stomach inflammation ( J:163367 )

• acute and chronic in antral polyps of tamoxifen-treated mice

integument

alopecia ( J:163367 )

• in tamoxifen-treated mice

Genotype
MGI:3811322

cn12

• Allelic Composition: Bmpr1a^tm2.1Bhr/Bmpr1a⁺; Tg(Sftpc-cre)1Blh/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * DBA/2

respiratory system

respiratory system phenotype ( J:106392 )

N • Background Sensitivity: unlike on an ICR mixed background, all mice exhibit normal lung morphology

Genotype
MGI:3811314

cn13

• Allelic Composition: Bmpr1a^tm2.1Bhr/Bmpr1a⁺; Tg(Sftpc-cre)1Blh/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * DBA/2 * ICR

respiratory system

abnormal lung morphology ( J:106392 )

• Background Sensitivity: 46% of mice exhibit lung abnormalities between E16.5, and birth unlike when the transgene is carried on a C57BL/6 background

Genotype
MGI:3811312

cn14

• Allelic Composition: Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr; Tg(Sftpc-cre)1Blh/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * DBA/2 * ICR

mortality/aging

postnatal lethality, complete penetrance ( J:106392 )

• all mice die or are euthanized within 2 days of birth due to severe respiratory distress

respiratory system

respiratory system phenotype ( J:106392 )

N • despite defects in distal portions of the lungs, proximal bronchi and bronchioles appear normal

abnormal lung morphology ( J:106392 )

• at E16.5, the distal regions of all four lobes are abnormal

• lungs are highly abnormal with large, fluid-filled (emphysematous) sacs

• however, lungs are normal at E12.5

abnormal lung epithelium morphology ( J:106392 )

• at E16.5, the number of more distal branches is reduced and branches are smaller than in wild-type mice

• epithelial cells in the periphery of the lung have a more rounded morphology than in wild-type mice

• epithelial cells cultured in a mesenchyme-free system fail to undergo secondary branching, develop fewer or no buds and exhibit a collapsed and folded morphology compared to wild-type cultures

decreased type II pneumocyte number ( J:106392 )

• fewer than normal as determined by surfactant C expression

abnormal respiratory system physiology ( J:106392 )

• despite defects in distal portions of the lungs, proximal bronchi and bronchioles appear normal

respiratory distress ( J:106392 )

Genotype
MGI:3663711

cn15

• Allelic Composition: Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr; Tg(GATA6-cre)#Jbeb/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB

cardiovascular system

abnormal mitral valve cusp morphology ( J:111392 )

• 45% of 3-month old mutants show longer mitral septal leaflets

abnormal tricuspid valve morphology ( J:111392 )

• exhibit a premature disappearance of the myocardial layer in the tricuspid mural leaflet (present at E14.5 but absent at E15.5)

Ebstein's malformation of tricuspid valve ( J:111392 )

• the posterior annulus fibrosis is displaced downward into the right ventricular cavity in one of six mutants

abnormal tricuspid valve cusp morphology ( J:111392 )

• 36% of 3-month old mutants show longer tricuspid mural leaflets than control valves

decreased heart left ventricle muscle contractility ( J:111392 )

• 3-month old mutants show significantly decreased left ventricular (LV) ejection fraction and increased LV-end-systolic dimension and LV-end-diastolic dimension

mitral valve regurgitation ( J:111392 )

• show a 2-fold increase in left atrial pressure consistent with mitral insufficiency

abnormal impulse conducting system conduction ( J:111392 )

• isolated Langendorff perfused mutant hearts show a delta wave with abnormal surface ECG

• hearts with abnormal surface ECG show a base-to-apex activation pattern with evidence of a posterior paraseptal bypass tract

• the annulus fibrosus is disrupted resulting in ventricular preexcitation

absent PR interval ( J:111392 )

• 6 of 33 mutants, aged between 2 and 6 months, show absence of PR interval

muscle

decreased heart left ventricle muscle contractility ( J:111392 )

• 3-month old mutants show significantly decreased left ventricular (LV) ejection fraction and increased LV-end-systolic dimension and LV-end-diastolic dimension

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Ebstein anomaly		DOID:14289	OMIM:224700	J:111392
Wolff-Parkinson-White syndrome		DOID:384	OMIM:194200	J:111392

Genotype
MGI:3819176

cn16

• Allelic Composition: Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr; Tg(Cga-cre)3Sac/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:121318 )

• occurs at E12.5 likely due to heart defects

embryo

decreased embryo size ( J:121318 )

• embryos are smaller than wild-type littermates at prior to lethality

growth/size/body

decreased embryo size ( J:121318 )

• embryos are smaller than wild-type littermates at prior to lethality

endocrine/exocrine glands

abnormal pituitary gland development ( J:121318 )

abnormal Rathke's pouch development ( J:121318 )

• at E10.5 pouch is thin and underdeveloped compared to wild-type littermates

nervous system

abnormal pituitary gland development ( J:121318 )

abnormal Rathke's pouch development ( J:121318 )

• at E10.5 pouch is thin and underdeveloped compared to wild-type littermates

cardiovascular system

abnormal heart morphology ( J:121318 )

• embryos display heart defects

Genotype
MGI:3785772

cn17

• Allelic Composition: Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr; Tg(Col2a1-cre)1Bhr/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL

Skeletal abnormalities in Bmpr1b^tm1Kml/Bmpr1b^tm1Kml, Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Tg(Col2a1-cre)1Bhr/?, and Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Bmpr1b^tm1Kml/Bmpr1b^tm1Kml Tg(Col2a1-cre)1Bhr/? mice

mortality/aging

postnatal lethality ( J:97410 )

skeleton

decreased length of long bones ( J:97410 )

abnormal thoracic cage shape ( J:97410 )

• rib cage is flattened

small thoracic cage ( J:97410 )

• rib cage is smaller and flattened

chondrodystrophy ( J:97410 )

• generalized chondrodysplasia

delayed bone ossification ( J:97410 )

respiratory system

respiratory distress ( J:97410 )

• respiratory distress due to smaller and flattened rib cage

Genotype
MGI:2181350

cn18

• Allelic Composition: Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr; Tg(Pou3f4-cre)32Cren/0
• Genetic Background: involves: 129S7/SvEvBrd * CD-1

limbs/digits/tail

abnormal digit morphology ( J:73526 )

ectopic digits ( J:73526 )

• ectopic distal phalanges are sometimes found

polydactyly ( J:73526 )

• although reduced digits is typical, polydactyly sometimes occurs

syndactyly ( J:73526 )

• polysyndactyly is common

abnormal hindlimb morphology ( J:73526 )

• if hindlimbs are present then they are highly malformed

• loss of ventral structures of hindlimbs

absent hindlimb ( J:73526 )

• in many but not all animals

Genotype
MGI:2181351

cn19

• Allelic Composition: Bmpr1a^tm2.1Bhr/Bmpr1a⁺; Tg(Pou3f4-cre)32Cren/0
• Genetic Background: involves: 129S7/SvEvBrd * CD-1

normal phenotype

no abnormal phenotype detected ( J:73526 )

Genotype
MGI:3574977

cn20

• Allelic Composition: Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr; Bmpr1b^tm1Kml/Bmpr1b^tm1Kml; Tg(Six3-cre)69Frty/0
• Genetic Background: involves: 129S/SvEv

pigmentation

abnormal retina pigment epithelium morphology ( J:96964 )

• at E12.5 the margin of the pigment epithelium is rough and a ventral discontinuity of the pigment is seen

vision/eye

increased retina apoptosis ( J:96964 )

• beginning at E11.25-E11.50 excess apoptosis is seen throughout the retina

abnormal eye development ( J:96964 )

• around E11.5 a drastic reduction in cell proliferation is seen in the retina

• Atoh7 expression is not initiated at E11.5 suggesting a failure to initiate retinal neurogenesis

abnormal retina morphology ( J:96964 )

• beginning at E11.25-E11.50 the retinal neuroectoderm is thinner

abnormal retina pigment epithelium morphology ( J:96964 )

• at E12.5 the margin of the pigment epithelium is rough and a ventral discontinuity of the pigment is seen

anophthalmia ( J:96964 )

• eyes are small at E12.5 and absent at birth

cellular

increased retina apoptosis ( J:96964 )

• beginning at E11.25-E11.50 excess apoptosis is seen throughout the retina

Genotype
MGI:3574976

cn21

• Allelic Composition: Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr; Bmpr1b^tm1Kml/Bmpr1b⁺; Tg(Six3-cre)69Frty/0
• Genetic Background: involves: 129S/SvEv

vision/eye

abnormal retina ganglion cell morphology ( J:96964 )

• many dorsal retinal ganglion cell axons form ectopic termination zones

• eye size and retinal layer morphology are normal

nervous system

abnormal retina ganglion cell morphology ( J:96964 )

• many dorsal retinal ganglion cell axons form ectopic termination zones

• eye size and retinal layer morphology are normal

Genotype
MGI:3785771

cn22

• Allelic Composition: Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr; Bmpr1b^tm1Kml/Bmpr1b^tm1Kml; Tg(Col2a1-cre)1Bhr/?
• Genetic Background: involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6 * SJL

Skeletal abnormalities in Bmpr1b^tm1Kml/Bmpr1b^tm1Kml, Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Tg(Col2a1-cre)1Bhr/?, and Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Bmpr1b^tm1Kml/Bmpr1b^tm1Kml Tg(Col2a1-cre)1Bhr/? mice

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:97410 )

• lethality between E17.5 and birth, due to compression of internal organs and eventual heart failure

growth/size/body

short snout ( J:97410 )

• embryos develop short snouts

decreased fetal size ( J:97410 )

• mutants are reduced in size starting at E13.5

embryo

abnormal notochord morphology ( J:97410 )

• notochord at E14.5 is disorganized and is embedded within a layer of dense fibroblasts

skeleton

decreased radius size ( J:97410 )

• small radius

abnormal ulna morphology ( J:97410 )

• small ulna

abnormal vertebral column morphology ( J:97410 )

• vertebral column is completely absent at E14.5

abnormal chondrocyte morphology ( J:97410 )

• chondrocytes undergo random and disorganized hypertrophy at P0

abnormal skeleton development ( J:97410 )

abnormal vertebrae development ( J:97410 )

• no vertebrae form by E13.5

abnormal cartilage development ( J:97410 )

• cartilage elements exhibit reduced rates of proliferation from E13.5 to E16.5 and increased cell apoptosis

• cartilage elements are severely disorganized and do not produce cartilage specific extracellular matrix

abnormal chondrocyte differentiation ( J:97410 )

• chondrocyte differentiation is impaired, with appendicular and nasal cavity condensations remaining in a prechondrocytic state

• although cells in prechondrocytic condensations eventually differentiate, they do not undergo the organized differentiation program found in the growth plate

abnormal epiphyseal plate morphology ( J:97410 )

• the few cartilage condensations that do form are delayed in the prechondrocytic state and never form an organized growth plate

chondrodystrophy ( J:97410 )

• severe generalized chondrodysplasia

failure of endochondral bone ossification ( J:97410 )

• majority of skeletal elements that form through endochondral ossification are absent and the ones that form are rudimentary and malformed

limbs/digits/tail

decreased radius size ( J:97410 )

• small radius

abnormal ulna morphology ( J:97410 )

• small ulna

abnormal digit development ( J:97410 )

• digits by E14.5 have fully formed pericondria but cells within the cores do not exhibit prechondrocyte characteristics

short limbs ( J:97410 )

• embryos develop short limbs

short tail ( J:97410 )

• embryos develop short tails

craniofacial

short snout ( J:97410 )

• embryos develop short snouts

Genotype
MGI:3574975

cn23

• Allelic Composition: Bmpr1a^tm1Bhr/Bmpr1a^tm2.1Bhr; Tg(Six3-cre)69Frty/0
• Genetic Background: Not Specified

vision/eye

vision/eye phenotype ( J:96964 )

N • no overt eye abnormalities are seen, the retinal layers and retinotectal projections are normal