Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bmp4tm2Blh mutation
(1 available);
any
Bmp4 mutation
(21 available)
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mortality/aging
embryo
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• all embryos lacked an allantois
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reproductive system
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• absent primordial germ cells
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digestive/alimentary system
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• 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
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liver/biliary system
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• by the 20 somite stage some thickening of the foregut endoderm is seen but a distinct liver bud has not developed
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• by the 20 somite stage a distinct liver bud has not formed
• however, initiation of albumin expression is detected
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growth/size/body
cellular
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• absent primordial germ cells
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bmp4tm2Blh mutation
(1 available);
any
Bmp4 mutation
(21 available)
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mortality/aging
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• 82% of mice survive to weaning
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skeleton
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• 50% of mice have small or missing 13th rib
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• 50% of mice have small or missing 13th rib
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• 7 of 10 mice develop cervical and thoracic vertebral fusions
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• 7 of 10 mice develop cervical and thoracic vertebral fusions
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• 7 of 10 mice develop formation of the spinous processes in cervical and thoracic vertebra
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renal/urinary system
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• 8% of mice have polycystic or enlarged kidneys
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• 8% of mice have polycystic or enlarged kidneys
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vision/eye
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• 13% of mice have small or missing eyes
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• 13% of mice have small or missing eyes
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cardiovascular system
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• at E15 to E 17.5, 10% of mice exhibit a defect in closure of the membranous portion of the ventricular septum
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growth/size/body
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• 8% of mice have polycystic or enlarged kidneys
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• 8% of mice have polycystic or enlarged kidneys
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Allelic
Composition |
Bmp4tm2Blh/Bmp4+
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Genetic
Background |
involves: 129S6/SvEvTac * Black Swiss |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bmp4tm2Blh mutation
(1 available);
any
Bmp4 mutation
(21 available)
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reproductive system
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• reduced number of primordial germ cells
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cellular
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• reduced number of primordial germ cells
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Allelic
Composition |
Bmp4tm2Blh/Bmp4+
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Genetic
Background |
involves: 129S6/SvEvTac * Black Swiss * C57BL/6J |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bmp4tm2Blh mutation
(1 available);
any
Bmp4 mutation
(21 available)
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renal/urinary system
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• 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
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• small kidney with regions devoid of nephrogenic components that are instead filled with cysts and stromal mesenchymal cells
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• at E12.5, the number of condensed mesenchyme per kidney is reduced; however, nephron density per se is not noticeably reduced
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• at E16.5, condensed and noninduced mesenchymal cells are reduced in number
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• 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
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• 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)
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• dilated caliceal space with thinning of the renal parenchyma
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• ureterovesical junction-type hydronephrosis is seen in 32% of mice with gross abnormalities
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• 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
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• 60% of mice with gross anomalies show variably reduced kidney mass with microscopically dysplastic regions
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• 8% of mice with gross anomalies show duplex kidney with bifid ureter
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• at E16.5 and P0, ureters are dilated with abnormal winding and kinking in the middle portions
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• 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)
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• 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
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• 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
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• in the most severely affected embryos the ureter fails to connect to the bladder, connecting instead to the seminal vesicles or vas deferens
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• accompanies hydronephrosis
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• ectopic ureterovesical (UV) junction
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• 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
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• 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
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• 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
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embryo
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• 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
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• at E12.5, the common mesonephric duct is longer compared to wild-type controls
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cellular
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• 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
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growth/size/body
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• small kidney with regions devoid of nephrogenic components that are instead filled with cysts and stromal mesenchymal cells
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Allelic
Composition |
Bmp4tm2Blh/Bmp4+
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Genetic
Background |
involves: 129S6/SvEvTac * ICR |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bmp4tm2Blh mutation
(1 available);
any
Bmp4 mutation
(21 available)
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cardiovascular system
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• 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
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• 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
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• proportion of proliferating vascular smooth muscle cells is decreased in hypoxic mutants compared to hypoxic wild-type mice
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• 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
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• 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
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• under hypoxic conditions, peripheral microvascular endothelial cells do not secrete BMP4 in contrast to cultured wild-type cells
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muscle
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• proportion of proliferating vascular smooth muscle cells is decreased in hypoxic mutants compared to hypoxic wild-type mice
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• 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
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growth/size/body
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• 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
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Allelic
Composition |
Bmp4tm1.1Jlch/Bmp4tm2Blh
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Genetic
Background |
involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6 |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bmp4tm1.1Jlch mutation
(0 available);
any
Bmp4 mutation
(21 available)
Bmp4tm2Blh mutation
(1 available);
any
Bmp4 mutation
(21 available)
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mortality/aging
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• 37% of mice are recovered between E12 and P0 versus the expected 50%
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• 25% of the expected ratio of mice survive to weaning
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embryo
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• 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
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• 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
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skeleton
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• in 3 of 3 mice at E13.5 to P0
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limbs/digits/tail
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• 1 in 12 mice display polydactyly at a similar frequency as in Bmp4tm1.1Jlch homozygotes
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• 8 of 12 mice exhibit forelimb postaxial duplications at a similar frequency as in Bmp4tm1.1Jlch homozygotes
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cardiovascular system
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• at E15 to E 17.5, 50% of mice exhibit a defect in closure of the membranous portion of the ventricular septum
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vision/eye
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• at E12 to P0, 13 of 22 mice have missing or smaller eyes
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• at E12 to P0, 13 of 22 mice have missing or smaller eyes
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growth/size/body
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• in 9 of 18 mice at E13.5 to P0
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• 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)
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Allelic
Composition |
Bmp4tm2Blh/Bmp4+
Nogtm1Amc/Nog+
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Genetic
Background |
involves: 129S1/Sv * 129S6/SvEvTac |
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normal phenotype
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• embryos show no abnormal phenotype
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nervous system
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N |
• at E14, neural tube is closed, showing partial phenotypic rescue of neural tube defect seen in Nog-null embryos
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skeleton
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• at E17, lumbar vertebrae are more developed than in Nog-null embryos
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• neural arches are present but noticeably dysmorphic
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embryo
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• yolk sacs are avascular
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cardiovascular system
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• yolk sacs are avascular
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Allelic
Composition |
Bmp4tm2Blh/Bmp4+
Bmpertm1Ysas/Bmper+
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Genetic
Background |
involves: 129S6/SvEvTac * C57BL/6 * CBA |
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vision/eye
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• 18% exhibit microphthalmia
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skeleton
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N |
• do not exhibit a vertebral phenotype
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skeleton
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• exhibit suppression of vertebral arch development, a more severe defect than seen in single Bmper homozygotes
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• exhibit a reduction in the ossification of vertebral bodies that is more severe than seen in single Bmper homozygotes
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• exhibit a reduction in size of the vertebral body that is more severe than seen in single Bmper homozygotes
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vision/eye
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• exhibit an increase in the frequency of microphthalmia with 100% of double mutants showing the phenotype compared to 18% of double heterozygous mutants
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bmp4tm2Blh mutation
(1 available);
any
Bmp4 mutation
(21 available)
Twsg1tm1.1Mboc mutation
(0 available);
any
Twsg1 mutation
(20 available)
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craniofacial
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N |
• no external craniofacial defects between E13.5 and E16.5
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Analysis Tools