Mouse Genome Informatics
hm1
    Bmp4tm1Blh/Bmp4tm1Blh
129S2/SvPas-Bmp4tm1Blh
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• none survive beyond the egg cylinder stage

embryogenesis
• absence of organized primitive streak
• hypoplastic extraembryonic mesoderm: small amount can be distinguished


Mouse Genome Informatics
hm2
    Bmp4tm1Blh/Bmp4tm1Blh
B6.129S2-Bmp4tm1Blh/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• none survive beyond the egg cylinder stage

embryogenesis
• absence of organized primitive streak
• hypoplastic extraembryonic mesoderm: small amount can be distinguished
• there is a relative paucity of blood islands containing red blood cells in the visceral yolk sac

hematopoietic system
• few red blood cells are found in the heart, dorsal aorta, and vessels of an E8.5 embryo


Mouse Genome Informatics
hm3
    Bmp4tm1Blh/Bmp4tm1Blh
involves: 129S2/SvPas * 129S6/SvEvTac * Black Swiss
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• an abnormal posterior bulge is present from the headfold to 6 somite stage
• node is either flat or slightly convex with an irregular periphery in embryos from the headfold to 6 somite stage unlike in controls where it is concave
• one embryo had large endoderm-like cells within the node
• a mass of mesodermal cells extending to the apical surface of the ectoderm fills much of the posterior amniotic cavity
• at the 2 to 8 somite stage, over 75% of embryos show patch or reduced Nodal expression and lack expression in the left lateral plate mesoderm
• in about 65% of embryos at the 3 to 4 somite stage Lefty2 expression is absent from the lateral plate mesoderm
• much of the posterior amniotic cavity is filled up by a mass of mesodermal cells that extends to the apical surface of the ectoderm

cardiovascular system
• at the 9 to 10 somite stage in about 50% of embryos the heart tube lies centrally along the midline and shows no signs of looping


Mouse Genome Informatics
hm4
    Bmp4tm1Blh/Bmp4tm1Blh
involves: 129S2/SvPas * Black Swiss
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

growth/size/body
• at E10.5, homozygotes have 20-27 somites, while littermates have greater than 35 (J:51570)

vision/eye
• failure of lens placode induction

embryogenesis
• all embryos lacked an allantois
• at E10.5, homozygotes have 20-27 somites, while littermates have greater than 35 (J:51570)

reproductive system

endocrine/exocrine glands
• no sign of Rathke's pouch formation (either ectodermal thickening or invagination) is noted at E9.5-E9.75

nervous system
• no sign of Rathke's pouch formation (either ectodermal thickening or invagination) is noted at E9.5-E9.75


Mouse Genome Informatics
hm5
    Bmp4tm1Blh/Bmp4tm1Blh
involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• animals die between E7.5 and E10.5; most are arrested at the egg cylinder stage

embryogenesis
• posterior patterning abnormalities
• absent extraembryonic mesoderm
• visceral yolk sac often have a "blebby" appearance attributable to the paucity of extraembryonic mesoderm and blood islands underlying the endoderm layer
• embryos that develop past the egg cylinder stage have a paucity of blood islands
• embryos are grossly retarded but have undergone turning, have a beating heart and forelimb buds

growth/size/body
• embryos are grossly retarded but have undergone turning, have a beating heart and forelimb buds


Mouse Genome Informatics
hm6
    Bmp4tm1Blh/Bmp4tm1Blh
involves: 129S2/SvPas * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

embryogenesis
• all embryos lacked an allantois

reproductive system
• absent primordial germ cells

growth/size/body


Mouse Genome Informatics
hm7
    Bmp4tm1Blh/Bmp4tm1Blh
involves: 129S2/SvPas * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• embryos die between E9.5-E11.5

growth/size/body
• are grossly retarded but have undergone turning, have a beating heart and forelimb buds

embryogenesis
• are grossly retarded but have undergone turning, have a beating heart and forelimb buds


Mouse Genome Informatics
ht8
    Bmp4tm1Blh/Bmp4+
B6.129S2-Bmp4tm1Blh/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Anterior eye segment abnormalities in Bmp4tm1Blh/Bmp4+ mice

mortality/aging
• less than half as many heterozygotes are born as expected

vision/eye
• Background Sensitivity: mutants on a C57BL/6J background exhibit variable anterior and posterior segment abnormalities that are reduced on a mixed C3Hf/HeA and C57BL/LiA background and are rarely seen in mutants on CAST/Ei, 129S6/SvEvTac, or BALB/cJ background
• variable anterior segment abnormalities in mutants 3-5 months of age
• abnormal in most eyes
• small or absent
• displaced Schwalbe's line
• hypoplastic or absent trabecular meshwork that appears compressed and stalled in development
• hypoplastic or absent trabecular meshwork that appears compressed and stalled in development
• pupils are often eccentrically located
• iris is generally normal, however in some eyes, the iris is hypoplastic and malformed; occasionally the malformation is extensive involving both iris and ciliary body
• extracellular matrix (ECM) abnormalities are seen in the peripheral cornea, showing irregularly arranged collagen bundles
• abnormal iridocorneal attachments (anterior synechiae) of variable extent
• peripheral cornea is often thinner with neovascularization
• some eyes exhibit scleralization (opacity) of the the peripheral cornea or diffuse corneal haze
• anterior subcapsular and cortical contaracts occur in most mutants
• anterior subcapsular and cortical contaracts occur in most mutants
• frequency increased 3 fold
• variable posterior eye segment abnormalities
• abnormalities of the optic nerve head are frequently observed
• optic nerve abnormalities range from normal to absent, and are most often severely abnormal consisting of loose connective tissue, with absence of neural tissue
• the optic nerve is sometimes absent
• the main retinal vessels branch close to the optic nerve and are irregularly arranged compared to wild-type
• retinal ganglion cell layer on average contains about 50% the normal number of cells
• photoreceptor layer typically appears normal, however there are foci of retinal dysplasia, characterized by rosette formation
• about 25% of heterozygotes exhibit retinal detachment as early as P30, with increased incidence as mice age
• dense network of small tortuous vessels throughout the vitreous that leak fluorescein, indicating compromised integrity of the vessels
• abnormal persistence of the anterior hyaloid vessels
• posterior hyaloid vessels persist throughout the 17 month period studied and increase in number and size beyond that normally seen at birth
• irregular white patches in the vitreous and dense vitreous haze in the majority of eyes
• frequency increased 3 fold
• in some eyes, both a- and b-wave amplitude are reduced, due in part to poor pupillary dilation, with preferential loss of b-wave relative to a-wave
• mutants with severe drainage structure abnormalities over 80% or more of their angle's extent have elevated intraocular pressure

hearing/vestibular/ear
• circling heterozygotes display low gain ratios with yaw axis rotation in the vestibulo-collic reflex, indicating poorer head stability relative to wild-type mice; poor response is consistent with horizontal semicircular canal dysfunction
• in the pitch axis, circling heterozygotes display as good or better head stability than wild-type mice, with gain ratios being greater or equal to 1
• in contrast, non-circling heterozygotes have gain ratios of greater or equal to 1 in both the yaw and pitch axes, indicating normal VCR function
• 2 of 4 circler and 2 of 4 non-circler heterozygotes show reduced neuronal processes in the organ of Corti
• in contrast, the saccule, utricle and ampullae of heterozygotes show normal numbers of neuronal processes
• 4 of 6 circling heterozygotes display a significantly reduced number of stereocilia in their ampullae relative to wild-type; the other two circlers show a patchy decrease in the number of stereocilia
• in contrast, circling heterozygotes show normal stereocilia in the organ of Corti, saccule and utricle
• non-circling heterozygotes have normal-appearing stereocilia in both auditory and vestibular tissues
• most circling heterozygotes exhibit elevated ABR thresholds across all test frequencies (7 out of 11 mice at 6 kHz and 12 kHz; 8 out of 11 mice at 24 kHz)
• non-circlers display elevated ABR thresholds similar to those of circlers
• both circling and non-circling heterozygotes display a partial hearing loss, as assessed by ABR testing

nervous system
• 4 of 6 circling heterozygotes display a significantly reduced number of stereocilia in their ampullae relative to wild-type; the other two circlers show a patchy decrease in the number of stereocilia
• in contrast, circling heterozygotes show normal stereocilia in the organ of Corti, saccule and utricle
• non-circling heterozygotes have normal-appearing stereocilia in both auditory and vestibular tissues
• neuronal processes innervating the cochlea of both circling and non-circling heterozygotes mice are reduced in number
• abnormalities of the optic nerve head are frequently observed
• optic nerve abnormalities range from normal to absent, and are most often severely abnormal consisting of loose connective tissue, with absence of neural tissue
• the optic nerve is sometimes absent

behavior/neurological
• circling heterozygotes display low gain ratios with yaw axis rotation in the vestibulo-collic reflex, indicating poorer head stability relative to wild-type mice; poor response is consistent with horizontal semicircular canal dysfunction
• in the pitch axis, circling heterozygotes display as good or better head stability than wild-type mice, with gain ratios being greater or equal to 1
• in contrast, non-circling heterozygotes have gain ratios of greater or equal to 1 in both the yaw and pitch axes, indicating normal VCR function
• by 2 weeks of age, 10% of heterozygous pups display circling behavior
• 1 of 2 circlers spent 50% of the time circling in a clockwise direction, 17% in a counterclockwise direction and 33% not circling
• the second circler spent 65% of the time circling in a clockwise direction, 1% in a counterclockwise direction and 34% not circling

reproductive system
• sometimes cystic (J:42445)
• sometimes with abnormal lobulation (J:42445)
• sometimes cystic (J:42445)
• female heterozygotes are poorer breeders relative to wild-type females (J:118380)
• average litter from mating a wild-type C57BL/6 mouse with a C57BL/6 heterozygote yields only 1 heterozygous pup

cardiovascular system
• the main retinal vessels branch close to the optic nerve and are irregularly arranged compared to wild-type

renal/urinary system
• marked hydronephrosis in 12% of heterozygotes but ureter is undilated
• cortex of remaining kidney is atrophic
• single cystic kidney in about 12% of heterozygotes
• multiple cysts involving both tubules and glomeruli
• single cystic kidney in about 12% of heterozygotes

craniofacial
• in about 12% of individuals
• in about 12% of individuals

limbs/digits/tail
• 12% with unilateral anterior polydactyly involving the right hind limb only

skeleton
• in about 12% of individuals
• in about 12% of individuals

endocrine/exocrine glands
• sometimes cystic (J:42445)
• sometimes with abnormal lobulation (J:42445)
• sometimes cystic (J:42445)

Mouse Models of Human Disease
OMIM IDRef(s)
Axenfeld-Rieger Syndrome, Type 3; RIEG3 602482 J:82877


Mouse Genome Informatics
ht9
    Bmp4tm1Blh/Bmp4+
involves: 129S2/SvPas * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• Background Sensitivity: incidence of eye abnormalities is much lower on the 129S6/SvEvTac background than on a C57BL/6J background, with only 1 of 12 mice showing persistent vitreous vessels and abnormal pupil/iris
• 1 of 12 mice shows persistent vitreous vessels
• 1 of 12 mice shows abnormal pupil/iris

reproductive system
• fewer primordial germ cells due to a reduced founder population rather than impaired expansion
• estimated 55% reduction in PGC founder population of mice on the 129S/SvEv, Black Swiss mixed background


Mouse Genome Informatics
ht10
    Bmp4tm1Blh/Bmp4+
involves: 129S2/SvPas * 129S6/SvEvTac * Black Swiss
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• Background Sensitivity: mice do not display circling behavior on Black Swiss background but a small percentage do on a C57BL/6 background (J:136636)


Mouse Genome Informatics
ht11
    Bmp4tm1Blh/Bmp4+
involves: 129S2/SvPas * BALB/cJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• Background Sensitivity: only 1 out of 15 mice on a BALB/cJ background exhibit eye abnormalities (persistent vitreous vessels) compared to multiple and variable eye abnormalities seen on a C57BL/6J background


Mouse Genome Informatics
ht12
    Bmp4tm1Blh/Bmp4+
involves: 129S2/SvPas * C3Hf/HeA * C57BL/LiA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• Background Sensitivity: on a C3Hf/HeA and C57BL/LiA background, fewer mutants exhibit anterior segment abnormalities, with only half showing defects compared to 2/3 of mutants on a C57BL/6J background
• 5 of 13 mutants exhibit enlarged pupils


Mouse Genome Informatics
ht13
    Bmp4tm1Blh/Bmp4+
involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
• diabetic mutants (generated by treatment with streptozotocin, STZ) exhibit decreased body weight compared to untreated controls

hearing/vestibular/ear
N
• mice exhibit normal hearing (J:159227)
• at E12, mice exhibit small or absent lateral plate epithelium compared with wild-type mice with the central part least affected of all the parts
• higher in the left ear than the right ear
• Background Sensitivity: 70% of females and 62% of males on a mixed 129S2/SvPas and C57BL/6 background exhibit abnormal semicircular canal compared to only 9% of mice on a mixed 129S2/SvPas, C57BL/6, and CBA background
• the lateral duct and cartilage lining are absent in some mice
• partially truncated, constricted, or absent in some mice

behavior/neurological
• in 37% of females and 24% of males strongly associated with bilateral defects in the lateral semicircular canal

homeostasis/metabolism
• diabetic mutants (generated by treatment with streptozotocin, STZ) have increased blood glucose similar to STZ-treated wild-type mice

renal/urinary system
• mice show attenuation of mesangial expansion compare to diabetic (STZ-treated) wild-type


Mouse Genome Informatics
ht14
    Bmp4tm1Blh/Bmp4+
involves: 129S2/SvPas * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• fewer PGCs due to a reduced founder population rather than impaired expansion (J:53311)
• estimated 62% reduction in PGC founder population of mice on the C57BL/6, CBA mixed background (J:53311)
• PGCs were absent in 9% of mutant mice on the C57BL/6, CBA mixed background (J:53311)
• fewer Dppa3+ primordial germ cells than in wild-type mice (J:199855)

behavior/neurological
• in 22 of 60 of mice with bilateral lateral semicircular canal defects

hearing/vestibular/ear
• Background Sensitivity: only 9% of mice exhibit abnormal semicircular canal on a mixed 129S2/SvPas, C57BL/6, and CBA background compared to 70% of females and 62% of males on a mixed 129S2/SvPas and C57BL/6 background


Mouse Genome Informatics
ht15
    Bmp4tm1Blh/Bmp4+
involves: 129S2/SvPas * CAST/Ei
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• Background Sensitivity: on a CAST/Ei background, only one of seven mice develops a cataract compared to multiple and variable eye abnormalities in mice on a C57BL/6J background


Mouse Genome Informatics
ht16
    Bmp4tm1Blh/Bmp4tm3.1Blh
involves: 129S2/SvPas * 129S6/SvEvTac * Black Swiss
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• animals at E17.5 have no apparent defects other than eye dysmorphology, but no live births are noted

vision/eye


Mouse Genome Informatics
ht17
    Bmp4tm1Blh/Bmp4tm4Blh
involves: 129S2/SvPas * 129S6/SvEvTac * Black Swiss * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• percentage of mice display lateral canal truncation


Mouse Genome Informatics
ht18
    Bmp4tm1Blh/Bmp4tm3.1Blh
involves: 129S2/SvPas * 129S6/SvEvTac * Black Swiss * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die between P1 and P7

cardiovascular system
N
• no outflow tract abnormalities are seen (J:86001)
• severe atrial septum primum abnormality resulting in an ostium primum atrial septation defect or partial atrial ventricular canal defect
• however, the atrioventicular and ventricular septa are similar to controls

vision/eye
• lack normal eyes


Mouse Genome Informatics
cn19
    Bmp4tm1Blh/Bmp4tm4Blh
Foxg1tm1(cre)Skm/Foxg1+

involves: 129 * Black Swiss * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• cochlear ducts show variability in length
• less severely affected embryos display truncation of lateral canals
• not discernible in most severely affected embryos at E13.5
• not discernible in most severely affected embryos at E13.5
• malformed in most severely affected embryos at E13.5; intact endolymphatic duct only is evident in dorsal region of inner ear
• malformed in most severely affected embryos at E13.5; intact endolymphatic duct only is evident in dorsal region of inner ear


Mouse Genome Informatics
cn20
    Bmp4tm1Blh/Bmp4tm3.1Blh
Tg(Tnnt2-cre)5Blh/0

involves: 129S/Sv * Black Swiss * C57BL/6 * DBA/2 * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• no neonates are found

cardiovascular system
• at E12.5 about a 20% decrease in proliferation is detected in the atrioventricular cushions but not in other areas of the heart
• present in 80% of embryos at E15.5 - E16.5
• single atrioventricular junction with a common valve

Mouse Models of Human Disease
OMIM IDRef(s)
Atrioventricular Septal Defect; AVSD 606215 J:86001


Mouse Genome Informatics
cn21
    Bmp4tm1Blh/Bmp4tm4Blh
Tg(Pax2-cre)1Dje/0

involves: 129S2/SvPas * 129S6/SvEvTac * Black Swiss * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• tow thirds of embryos have inner ear defects; more mildly affected embryos show defects in the three ampullae and canals
• canal defects (in addition to lateral canal truncations) are observed in mildly affected embryos
• malformed in more severely affected embryos
• malformed in more severely affected embryos


Mouse Genome Informatics
cx22
    Bmp4tm1Blh/Bmp4+
Bmp8btm1Blh/Bmp8b+

involves: 129/Sv * 129S2/SvPas * Black Swiss
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• number of primordial germ cells is lower than in wild-type, but similar to numbers seen in Bmpb8 heterozygotes


Mouse Genome Informatics
cx23
    Bmp4tm1Blh/Bmp4+
Gpc3Gt(Ex136)Byg/Y

involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
limbs/digits/tail
• bifurcated 5th digits frequently seen on forelimbs (J:64330)
• ectopic triphalangeal duplications branching from the 5th metatarsal (J:64330)
• 66% show show similar branched bifurcation of the right 5th digit of the hind limb (J:64330)

skeleton
• dual ossification centers along the length of the sternum (J:64330)
• deformed (J:64330)
(J:64330)


Mouse Genome Informatics
cx24
    Bmp4tm1Blh/Bmp4+
Ctdnep1tm1Ryn/Ctdnep1tm1Ryn

involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• severely reduced as in Ctdnep1tm1Ryn homozygotes


Mouse Genome Informatics
cx25
    Bmp4tm1Blh/Bmp4+
Tg(Prdm14-Venus)1Sait/0

involves: 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• both the total number of primordial germ cells and YFP positive primordial germ cells are reduced compared to in wild-type mice


Mouse Genome Informatics
cx26
    Alx4tm1Rwi/Alx4+
Bmp4tm1Blh/Bmp4+

involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
limbs/digits/tail
• all double heterozygotes exhibit ectopic anterior digits only on the hindlimbs
• extra digit extends from a duplicated metatarsal
• extra digits are triphalangeal
• post axial "nubbins" also seen on the forelimbs of 80% of heterozygotes


Mouse Genome Informatics
cx27
    Bmp4tm1Blh/Bmp4+
Bmp7tm1Kry/Bmp7+

involves: 129S2/SvPas * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
N
• double heterozygotes are viable, fertile and have normal size and weight (J:48538)
• double heterozygotes have normal size and shape of internal organs and of long bones (J:48538)

limbs/digits/tail
• in one case, digit I was partially triplicated, showing both a complete duplication and a biphalangeal extension of the most anterior extra digit I
• in all cases, none of the extra digits show more than two phalanges but always look like digit I
• no webbing is observed in the affected limbs of double heterozygotes
• duplication of the first digit is found at a much higher frequency (50%) in double heterozygotes compared to single Bmp4tm1Blh heterozygotes (18%) or Bmp7 heterozygotes (0%); the penetrance of this duplication is, however, lower in double heterozygotes than in Bmp7 homozygous null mice (67%)
• both in Bmp7 homozygous null mice and double heterozygotes, polydactyly primarily affects the right hindlimb than the left hind- or forelimb; however, effects are also observed bilaterally
• most double heterozygotes exhibit incomplete duplication, and the extra digit extends from metatarsal I

skeleton
• 44% of double heterozygotes display rib cage defects, including multiple misalignment of the rib pairs
• as a result of asymmetric rib attachment, the sternum has a sinusoidal appearance in severely affected mice
• 11% of double heterozygotes have an abnormal xiphoid process: both the cartilaginous and ossified part of the xiphoid process are split medially
• 44% of double heterozygotes display multiple misalignment of the rib pairs
• 11% of double heterozygotes display fusion of the ribs; this defect always affects two consecutive costal elements and appears to be limited to a single pair of ribs


Mouse Genome Informatics
cx28
    Bmp4tm1Blh/Bmp4+
Gpc3tm1Snd/Y

involves: 129S2/SvPas * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
limbs/digits/tail
• bifurcated 5th digits frequently seen on forelimbs (J:64330)
• ectopic triphalangeal duplications branching from the 5th metatarsal (J:64330)
• 66% show show similar branched bifurcation of the right 5th digit of the hind limb (J:64330)

skeleton
• dual ossification centers along the length of the sternum (J:64330)
• deformed (J:64330)
(J:64330)


Mouse Genome Informatics
cx29
    Bmp4tm1Blh/Bmp4+
Twsg1tm1Emdr/Twsg1tm1Emdr

involves: 129S2/SvPas * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• severe head malformations with 64% penetrance
• phenotype similar in newborns and at E15.5
• low "implantation" of external ears

hearing/vestibular/ear
• low "implantation" of external ears

limbs/digits/tail
• caudal vertebrae shorter than normal and bone is less dense
• 2 centers of ossification in tail vertebrae and asymmetrical growth leads to kinks
• by E15.5, vertebral bodies of tail were narrower and more rectangular, fewer differentiated chondrocytes
• 80% of homozygotes with multiple kinks

respiratory system

skeleton
• caudal vertebrae shorter than normal and bone is less dense
• 2 centers of ossification in tail vertebrae and asymmetrical growth leads to kinks
• by E15.5, vertebral bodies of tail were narrower and more rectangular, fewer differentiated chondrocytes

vision/eye
• lens did not develop
• retina did not develop

nervous system
• single cavity, lack of ventricle medial wall (holoprosencephaly)
• malformed prosencephalon
• thickened basal diencephalons at the level of the hypothalamus
• lateral ganglionic eminence is missing

digestive/alimentary system

growth/size/body
• low "implantation" of external ears


Mouse Genome Informatics
cx30
    Bmp4tm1Blh/Bmp4+
Gli3Xt-J/Gli3+

involves: 129S2/SvPas * C3H/HeJ * C57BL/6J * C57BL/6NHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
limbs/digits/tail
• apoptotic area in the preaxial mesoderm is completely absent at 12.5 days
• post axial apoptotic areas are normal
• 100% with unilateral anterior polydactyly involving the hind limbs only
• defect extends into the metatarsals