Phenotypes associated with this allele

• Allele Symbol: Bmp4^tm2Blh
• Allele Name: targeted mutation 2, Brigid L Hogan
• Allele ID: MGI:2158495
• Summary: 12 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Bmp4^tm2Blh/Bmp4^tm2Blh	involves: 129S6/SvEvTac * Black Swiss	MGI:2664351
ht2	Bmp4^tm2Blh/Bmp4^+	B6.129S6-Bmp4^tm2Blh	MGI:3717208
ht3	Bmp4^tm2Blh/Bmp4^+	involves: 129S6/SvEvTac * Black Swiss	MGI:2664352
ht4	Bmp4^tm2Blh/Bmp4^+	involves: 129S6/SvEvTac * Black Swiss * C57BL/6J	MGI:3811541
ht5	Bmp4^tm2Blh/Bmp4^+	involves: 129S6/SvEvTac * ICR	MGI:3817971
ht6	Bmp4^tm1.1Jlch/Bmp4^tm2Blh	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6	MGI:3717209
cx7	Bmp4^tm2Blh/Bmp4^+ Nog^tm1Amc/Nog^+	involves: 129S1/Sv * 129S6/SvEvTac	MGI:3818001
cx8	Bmp4^tm2Blh/Bmp4^+ Nog^tm1Amc/Nog^tm1Amc	involves: 129S1/Sv * 129S6/SvEvTac	MGI:3818000
cx9	Bmp4^tm2Blh/Bmp4^+ Smo^tm1Amc/Smo^tm1Amc	involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6	MGI:3818885
cx10	Bmp4^tm2Blh/Bmp4^+ Bmper^tm1Ysas/Bmper^+	involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:3692275
cx11	Bmp4^tm2Blh/Bmp4^+ Bmper^tm1Ysas/Bmper^tm1Ysas	involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:3692274
cx12	Bmp4^tm2Blh/Bmp4^+ Twsg1^tm1.1Mboc/Twsg1^tm1.1Mboc	involves: 129S/SvEv * C57BL/6 * FVB/N	MGI:3830686

Genotype
MGI:2664351

hm1

• Allelic Composition: Bmp4^tm2Blh/Bmp4^tm2Blh
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:71204 )

• die at about E9.5

embryo

embryonic growth retardation ( J:53311 )

absent allantois ( J:53311 )

• all embryos lacked an allantois

reproductive system

absent primordial germ cells ( J:53311 )

• absent primordial germ cells

digestive/alimentary system

abnormal foregut morphology ( J:71204 )

• do not display thickening of the foregut endoderm at the 14-17 somite stage

• by the 20 somite stage some thickening is seen but a distinct liver bud has not developed

liver/biliary system

abnormal liver bud morphology ( J:71204 )

• by the 20 somite stage some thickening of the foregut endoderm is seen but a distinct liver bud has not developed

delayed hepatic development ( J:71204 )

• by the 20 somite stage a distinct liver bud has not formed

• however, initiation of albumin expression is detected

growth/size/body

embryonic growth retardation ( J:53311 )

cellular

absent primordial germ cells ( J:53311 )

• absent primordial germ cells

Genotype
MGI:3717208

ht2

• Allelic Composition: Bmp4^tm2Blh/Bmp4⁺
• Genetic Background: B6.129S6-Bmp4^tm2Blh

mortality/aging

postnatal lethality, incomplete penetrance ( J:108516 )

• 82% of mice survive to weaning

skeleton

decreased rib number ( J:108516 )

• 50% of mice have small or missing 13th rib

short ribs ( J:108516 )

• 50% of mice have small or missing 13th rib

thoracic vertebral fusion ( J:108516 )

• 7 of 10 mice develop cervical and thoracic vertebral fusions

cervical vertebral fusion ( J:108516 )

• 7 of 10 mice develop cervical and thoracic vertebral fusions

abnormal vertebral spinous process morphology ( J:108516 )

• 7 of 10 mice develop formation of the spinous processes in cervical and thoracic vertebra

renal/urinary system

polycystic kidney ( J:108516 )

• 8% of mice have polycystic or enlarged kidneys

enlarged kidney ( J:108516 )

• 8% of mice have polycystic or enlarged kidneys

vision/eye

microphthalmia ( J:108516 )

• 13% of mice have small or missing eyes

anophthalmia ( J:108516 )

• 13% of mice have small or missing eyes

cardiovascular system

perimembraneous ventricular septal defect ( J:108516 )

• at E15 to E 17.5, 10% of mice exhibit a defect in closure of the membranous portion of the ventricular septum

growth/size/body

polycystic kidney ( J:108516 )

• 8% of mice have polycystic or enlarged kidneys

enlarged kidney ( J:108516 )

• 8% of mice have polycystic or enlarged kidneys

Genotype
MGI:2664352

ht3

• Allelic Composition: Bmp4^tm2Blh/Bmp4⁺
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss

reproductive system

decreased primordial germ cell number ( J:53311 )

• reduced number of primordial germ cells

cellular

decreased primordial germ cell number ( J:53311 )

• reduced number of primordial germ cells

Genotype
MGI:3811541

ht4

• Allelic Composition: Bmp4^tm2Blh/Bmp4⁺
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss * C57BL/6J

renal/urinary system

abnormal renal/urinary system morphology ( J:61482 )

• at birth, 53% have grossly identifiably anomalies in the kidneys and urinary tract of these 47% are on the right side only, 15% are on the left side only and 38% are bilateral

kidney cyst ( J:61482 )

• small kidney with regions devoid of nephrogenic components that are instead filled with cysts and stromal mesenchymal cells

abnormal kidney development ( J:61482 )

abnormal kidney mesenchyme morphology ( J:61482 )

• at E12.5, the number of condensed mesenchyme per kidney is reduced; however, nephron density per se is not noticeably reduced

abnormal metanephric mesenchyme morphology ( J:82895 )

• at E16.5, condensed and noninduced mesenchymal cells are reduced in number

increased metanephric mesenchyme apoptosis ( J:82895 )

• at E14.5, a significantly higher number of apoptotic (TUNEL+) cells is detected in the stromal cell population of metanephric mesenchyme, unlike in wild-type controls

abnormal nephrogenic zone morphology ( J:61482 , J:82895 )

• at E14.5, in small kidneys the superficial nephrogenic zone is always thinner with a reduced number of nephrogenic components (J:61482)

• at E16.5, superficial nephrogenic components are lacking; however, the apoptotic activity in the nephrogenic zone is similar to that of wild-type controls (J:82895)

dilated kidney calyx ( J:61482 )

• dilated caliceal space with thinning of the renal parenchyma

hydronephrosis ( J:61482 )

• ureterovesical junction-type hydronephrosis is seen in 32% of mice with gross abnormalities

small kidney ( J:61482 )

• small kidney with regions devoid of nephrogenic components that are instead filled with cysts and stromal mesenchymal cells

• difference in kidney size is detectable at E14.5

renal hypoplasia ( J:61482 )

• 60% of mice with gross anomalies show variably reduced kidney mass with microscopically dysplastic regions

duplex kidney ( J:61482 )

• 8% of mice with gross anomalies show duplex kidney with bifid ureter

abnormal ureter morphology ( J:61482 )

• at E16.5 and P0, ureters are dilated with abnormal winding and kinking in the middle portions

abnormal ureter development ( J:61482 , J:82895 )

• at E13.5, the ureter still drains into the Wolffian duct unlike in wild-type controls (J:61482)

• at E15.5, smooth muscle development of the ureter is impaired; however, the size of the ureter lumen and morphology of the ureter epithelium remain normal (J:82895)

abnormal ureter smooth muscle morphology ( J:82895 )

• at E15.5, the % of alpha-SMA-expressing smooth muscle cells against total mesenchymal cells around the epithelium at the most cranial portion of the ureter is significantly lower than that in wild-type controls

bifid ureter ( J:61482 )

• 8% of mice with gross anomalies show duplex kidney with bifid ureter

• arise from duplex kidney and unite caudally to form a single ureter that drains into the bladder

dilated ureter ( J:61482 )

• variably dilated

ectopic ureter ( J:61482 )

• in the most severely affected embryos the ureter fails to connect to the bladder, connecting instead to the seminal vesicles or vas deferens

hydroureter ( J:61482 )

• accompanies hydronephrosis

abnormal ureterovesical junction morphology ( J:61482 )

• ectopic ureterovesical (UV) junction

abnormal ureteral orifice morphology ( J:61482 )

• at E16.5, ectopia of the ureterovesical orifice is observed, with the orifice located closer to the urethral orifice and the distance between the right and left ureteral orifices reduced

abnormal ureteric bud elongation ( J:61482 )

• at E11.5, the secondary buds are smaller

• at E11.5, both the main trunk and the stems of the first 2 branches of the ureter are significantly shorter

ectopic ureteric bud ( J:61482 )

• at E11.5, 2 of 19 mice had accessory buds forming from the main stem of the ureter

• at E11, the primary bud is positioned opposite the approximately 25th somite where in wild-type controls it is opposite the approximately 26th somite

embryo

increased metanephric mesenchyme apoptosis ( J:82895 )

• at E14.5, a significantly higher number of apoptotic (TUNEL+) cells is detected in the stromal cell population of metanephric mesenchyme, unlike in wild-type controls

abnormal Wolffian duct morphology ( J:61482 )

• at E12.5, the common mesonephric duct is longer compared to wild-type controls

cellular

increased metanephric mesenchyme apoptosis ( J:82895 )

• at E14.5, a significantly higher number of apoptotic (TUNEL+) cells is detected in the stromal cell population of metanephric mesenchyme, unlike in wild-type controls

growth/size/body

kidney cyst ( J:61482 )

• small kidney with regions devoid of nephrogenic components that are instead filled with cysts and stromal mesenchymal cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
urinary system disease		DOID:18		J:61482

Genotype
MGI:3817971

ht5

• Allelic Composition: Bmp4^tm2Blh/Bmp4⁺
• Genetic Background: involves: 129S6/SvEvTac * ICR

cardiovascular system

abnormal artery morphology ( J:112335 )

• after 3 weeks at 10% oxygen, medial wall thickness in muscularized arteries increases significantly in wild-type mice but is not observed in mutant arteries

abnormal angiogenesis ( J:112335 )

• after 3 weeks at 10% oxygen (hypoxia) , vascular remodeling results in medial wall thickening of muscularized arteries in wild-type mice but is not observed in mutant arteries

• increase in proportion of peripheral muscularized vessels observed in wild-type after hypoxia is significantly reduced in mutant animals exposed to hypoxic conditions

abnormal vascular smooth muscle morphology ( J:112335 )

• proportion of proliferating vascular smooth muscle cells is decreased in hypoxic mutants compared to hypoxic wild-type mice

heart right ventricle hypertrophy ( J:112335 )

• after 3 weeks of hypoxia, mice show significant attenuation of right ventricular hypertrophy compared to wild-type animals; after 5 weeks increase in right ventricle weight is attenuated relative to wild-type but not significantly different from mutants after 3 weeks of hypoxia

abnormal heart right ventricle pressure ( J:112335 )

• after 3 weeks of hypoxia, mice show little or no increase in right ventricular systolic pressure (RSVP ) compared to wild-type which display a markedly increased RSVP

• after 5 weeks of hypoxia, mutants show consistent fall in RSVP compared to value at 3 weeks of hypoxia

abnormal vascular endothelial cell physiology ( J:112335 )

• under hypoxic conditions, peripheral microvascular endothelial cells do not secrete BMP4 in contrast to cultured wild-type cells

muscle

abnormal vascular smooth muscle morphology ( J:112335 )

• proportion of proliferating vascular smooth muscle cells is decreased in hypoxic mutants compared to hypoxic wild-type mice

heart right ventricle hypertrophy ( J:112335 )

• after 3 weeks of hypoxia, mice show significant attenuation of right ventricular hypertrophy compared to wild-type animals; after 5 weeks increase in right ventricle weight is attenuated relative to wild-type but not significantly different from mutants after 3 weeks of hypoxia

growth/size/body

heart right ventricle hypertrophy ( J:112335 )

• after 3 weeks of hypoxia, mice show significant attenuation of right ventricular hypertrophy compared to wild-type animals; after 5 weeks increase in right ventricle weight is attenuated relative to wild-type but not significantly different from mutants after 3 weeks of hypoxia

Genotype
MGI:3717209

ht6

• Allelic Composition: Bmp4^tm1.1Jlch/Bmp4^tm2Blh
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:108516 )

• 37% of mice are recovered between E12 and P0 versus the expected 50%

postnatal lethality, incomplete penetrance ( J:108516 )

• 25% of the expected ratio of mice survive to weaning

embryo

abnormal allantois morphology ( J:108516 )

• at E8.5 to E9, 50% of mice exhibit an allantois that is not yet fused to the chorion and that contains a densely packed mesenchymal core

small allantois ( J:108516 )

• at E8.5 to E9

abnormal chorion morphology ( J:108516 )

• at E8.5 to E9, 50% of mice exhibit an allantois that is not yet fused to the chorion and that contains a densely packed mesenchymal core

skeleton

split xiphoid process ( J:108516 )

• in 3 of 3 mice at E13.5 to P0

limbs/digits/tail

polydactyly ( J:108516 )

• 1 in 12 mice display polydactyly at a similar frequency as in Bmp4^tm1.1Jlch homozygotes

abnormal forelimb morphology ( J:108516 )

• 8 of 12 mice exhibit forelimb postaxial duplications at a similar frequency as in Bmp4^tm1.1Jlch homozygotes

cardiovascular system

perimembraneous ventricular septal defect ( J:108516 )

• at E15 to E 17.5, 50% of mice exhibit a defect in closure of the membranous portion of the ventricular septum

vision/eye

microphthalmia ( J:108516 )

• at E12 to P0, 13 of 22 mice have missing or smaller eyes

anophthalmia ( J:108516 )

• at E12 to P0, 13 of 22 mice have missing or smaller eyes

growth/size/body

omphalocele ( J:108516 )

• in 9 of 18 mice at E13.5 to P0

failure of ventral body wall closure ( J:108516 )

• at E13.5 to P0, mice exhibit a variety of ventral body wall closure defects ranging from complete failure of ventral body wall fusion leading to the externalization of the viscera (in 5 of 18 mice), to umbilical hernia (in 9 of 18 mice) to the failure of sternal fusion leading to s split xiphoid process (in 3 of 3 mice)

Genotype
MGI:3818001

cx7

• Allelic Composition: Bmp4^tm2Blh/Bmp4⁺; Nog^tm1Amc/Nog⁺
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac

normal phenotype

no abnormal phenotype detected ( J:110617 )

• embryos show no abnormal phenotype

Genotype
MGI:3818000

cx8

• Allelic Composition: Bmp4^tm2Blh/Bmp4⁺; Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac

nervous system

nervous system phenotype ( J:110617 )

N • at E14, neural tube is closed, showing partial phenotypic rescue of neural tube defect seen in Nog-null embryos

skeleton

abnormal vertebrae development ( J:110617 )

• at E17, lumbar vertebrae are more developed than in Nog-null embryos

abnormal vertebral arch morphology ( J:110617 )

• neural arches are present but noticeably dysmorphic

Genotype
MGI:3818885

cx9

• Allelic Composition: Bmp4^tm2Blh/Bmp4⁺; Smo^tm1Amc/Smo^tm1Amc
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6

embryo

absent vitelline blood vessels ( J:128367 )

• yolk sacs are avascular

cardiovascular system

absent vitelline blood vessels ( J:128367 )

• yolk sacs are avascular

Genotype
MGI:3692275

cx10

• Allelic Composition: Bmp4^tm2Blh/Bmp4⁺; Bmper^tm1Ysas/Bmper⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

vision/eye

microphthalmia ( J:115338 )

• 18% exhibit microphthalmia

skeleton

skeleton phenotype ( J:115338 )

N • do not exhibit a vertebral phenotype

Genotype
MGI:3692274

cx11

• Allelic Composition: Bmp4^tm2Blh/Bmp4⁺; Bmper^tm1Ysas/Bmper^tm1Ysas
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

skeleton

abnormal vertebral arch development ( J:115338 )

• exhibit suppression of vertebral arch development, a more severe defect than seen in single Bmper homozygotes

abnormal vertebral body development ( J:115338 )

• exhibit a reduction in the ossification of vertebral bodies that is more severe than seen in single Bmper homozygotes

small vertebral body ( J:115338 )

• exhibit a reduction in size of the vertebral body that is more severe than seen in single Bmper homozygotes

vision/eye

microphthalmia ( J:115338 )

• exhibit an increase in the frequency of microphthalmia with 100% of double mutants showing the phenotype compared to 18% of double heterozygous mutants

Genotype
MGI:3830686

cx12

• Allelic Composition: Bmp4^tm2Blh/Bmp4⁺; Twsg1^tm1.1Mboc/Twsg1^tm1.1Mboc
• Genetic Background: involves: 129S/SvEv * C57BL/6 * FVB/N

craniofacial

craniofacial phenotype ( J:88784 )

N • no external craniofacial defects between E13.5 and E16.5