Phenotypes associated with this allele

• Allele Symbol: Tgfb2^tm1Doe
• Allele Name: targeted mutation 1, Thomas Doetschman
• Allele ID: MGI:1888389
• Summary: 17 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tgfb2^tm1Doe/Tgfb2^tm1Doe	involves: 129P2/OlaHsd	MGI:5008268
hm2	Tgfb2^tm1Doe/Tgfb2^tm1Doe	involves: 129P2/OlaHsd * Black Swiss	MGI:2668213
hm3	Tgfb2^tm1Doe/Tgfb2^tm1Doe	involves: 129P2/OlaHsd * C57BL/6	MGI:3848993
ht4	Tgfb2^tm1Doe/Tgfb2^+	involves: 129P2/OlaHsd	MGI:5008270
ht5	Tgfb2^tm1Doe/Tgfb2^+	involves: 129P2/OlaHsd * Black Swiss	MGI:2668214
ht6	Tgfb2^tm1Doe/Tgfb2^+	involves: 129/Sv * 129P2/OlaHsd * Black Swiss * C57BL/6J	MGI:3758329
ht7	Tgfb2^tm1Doe/Tgfb2^+	STOCK Tgfb2^tm1Doe/J	MGI:5444484
cn8	Ext1^tm1Yama/Ext1^+ H2az2^Tg(Wnt1-cre)11Rth/H2az2^+ Tgfb2^tm1Doe/Tgfb2^+	B6.Cg-Tgfb2^tm1Doe H2az2^Tg(Wnt1-cre)11Rth Ext1^tm1Yama	MGI:4360749
cx9	Tgfb2^tm1Doe/Tgfb2^+ Tgfb3^tm1Doe/Tgfb3^tm1Doe	involves: 129P2/OlaHsd	MGI:5008265
cx10	Tgfb2^tm1Doe/Tgfb2^tm1Doe Tgfb3^tm1Doe/Tgfb3^tm1Doe	involves: 129P2/OlaHsd	MGI:5008266
cx11	Tgfb2^tm1Doe/Tgfb2^tm1Doe Tgfb3^tm1Doe/Tgfb3^+	involves: 129P2/OlaHsd	MGI:5008267
cx12	Tgfb2^tm1Doe/Tgfb2^+ Tgfb3^tm1Doe/Tgfb3^+	involves: 129P2/OlaHsd	MGI:5008269
cx13	Fbn1^tm1Hcd/Fbn1^+ Tgfb2^tm1Doe/Tgfb2^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:5444488
cx14	Cdkn2a^tm1(GFP)Cjs/Cdkn2a^tm1(GFP)Cjs Tgfb2^tm1Doe/Tgfb2^tm1Doe	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6	MGI:3848994
cx15	Cdkn2a^tm1(GFP)Cjs/Cdkn2a^tm1(GFP)Cjs Tgfb2^tm1Doe/Tgfb2^+	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6	MGI:3848995
cx16	Cdkn2a^tm1Cjs/Cdkn2a^+ Tgfb2^tm1Doe/Tgfb2^tm1Doe	involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6	MGI:3848999
cx17	Cdkn2a^tm1Sxs/Cdkn2a^+ Tgfb2^tm1Doe/Tgfb2^tm1Doe	involves: 129/Sv * 129P2/OlaHsd * C57BL/6	MGI:3848997

Genotype
MGI:5008268

hm1

• Allelic Composition: Tgfb2^tm1Doe/Tgfb2^tm1Doe
• Genetic Background: involves: 129P2/OlaHsd

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

limbs/digits/tail

limbs/digits/tail phenotype ( J:76541 )

N • mice exhibit normal apoptosis of interdigital webbing

Genotype
MGI:2668213

hm2

• Allelic Composition: Tgfb2^tm1Doe/Tgfb2^tm1Doe
• Genetic Background: involves: 129P2/OlaHsd * Black Swiss

mortality/aging

neonatal lethality, complete penetrance ( J:41682 , J:73681 )

• live-born homozygotes respond to mechanical stimulation but generally die within minutes with respiratory distress (J:41682)

• homozygotes fail to survive beyond 2 hrs due to impaired cardiovascular function (J:73681)

perinatal lethality, incomplete penetrance ( J:41682 )

• two-thirds of homozygotes die shortly before or during birth and the remaining are born cyanotic

cardiovascular system

pulmonary artery hypoplasia ( J:103391 )

• 1 of 24 (4.2%) of homozygotes display a hypoplastic pulmonary artery

abnormal aorta morphology ( J:103391 )

• overall, 33.3% of homozygotes aged E13.5 to 18.5 display structural abnormalities of the aorta or its branches

• at E11.5-E16.5, increased apoptosis is noted in aortic segments deriving from the fourth arch

aberrant origin of the right subclavian artery ( J:103391 )

• 2 of 24 (8.3%) of homozygotes display an aberrant right subclavian artery

aortic arch hypoplasia ( J:103391 )

• 5 of 24 (20.8%) of homozygotes exhibit hypoplasia of the aortic arch and/or ascending aorta

interrupted aortic arch ( J:103391 )

• 2 of 24 (8.3%) of homozygotes exhibit interruption of the aortic arch

interrupted aortic arch, type b ( J:103391 )

• 1 of 24 (4.2%) of homozygotes with a common arterial trunk display interruption of the aortic arch type B

ascending aorta hypoplasia ( J:41682 , J:103391 )

• at E18.5, homozygotes exhibit a small, thin-walled, hypoplastic ascending aorta (J:41682)

• 5 of 24 (20.8%) of homozygotes exhibit hypoplasia of the aortic arch and/or ascending aorta (J:103391)

abnormal myocardium layer morphology ( J:41682 , J:103391 )

• at E18.5, the mutant myocardium is hypercellular and less trabeculated (J:41682)

• at E18.5, some homozygotes display normal myocardialization of outflow tract cushions; others exhibit absence of myocardialization, with only a small fibrous ridge below the semilunar valves (J:103391)

trabecula carnea hypoplasia ( J:41682 )

abnormal cardiovascular development ( J:103391 )

• overall, 87.5% (21 of 24) homozygous mutant embryos aged E13.5 to 18.5 display abnormalities of the heart and great vessels

persistent right dorsal aorta ( J:103391 )

• 1 of 24 (4.2%) of homozygotes display a remnant of the right dorsal aorta

abnormal cardiac outflow tract development ( J:103391 )

• at E11.5-E16.5, homozygotes display increased apoptosis in the outflow tract relative to wild-type embryos; apoptosis occurs 1 day later (E14.5), and decreases more slowly than normal

abnormal truncus arteriosus septation ( J:103391 )

• 1 of 24 (4.2%) of homozygotes display a common arterial trunk with interruption of the aortic arch type B

abnormal atrioventricular cushion morphology ( J:103391 )

• at E13.5, homozygotes exhibit a normal endocardial cushion volume; however, the normal decrease in total endocardial cushion volume observed in older (E15.5) wild-type embryos does not occur

failure of atrioventricular cushion closure ( J:103391 )

• in some cases, fusion of the proximal cushions is incomplete

• incomplete fusion of the endocardial cushions results in a small membranous VSD

• an extensive perimembranous inlet VSD is seen in cases in which outflow tract and AV cushions do not meet

failure of heart looping ( J:103391 )

• homozygotes display various degrees of failure of normal remodeling of the primitive heart e.g. overriding tricuspid valve and DORV interfering with final phase of cardiac looping and wedging

double outlet right ventricle ( J:41682 , J:103391 )

• at E18.5, 3 of 16 homozygotes exhibit DORV (J:41682)

• 79.2% (19 of 24) of homozygotes exhibit a DORV with different relative positions of the arterial orifices, i.e. posterior (13 of 19), side-by-side (3 of 19), or slightly anterior (3 of 19) to the pulmonary orifice (J:103391)

• all mutant hearts with DORV display a bilateral muscular conus (J:103391)

abnormal atrioventricular valve morphology ( J:41682 , J:103391 )

• at E18.5, both tricuspid and mitral valve are abnormally connected to the left ventricle (J:41682)

• 8 of 24 (33.3%) of homozygotes display AV valve thickening (J:103391)

thick mitral valve ( J:103391 )

• 3 of 24 (12.5%) of homozygotes with tricuspid valve thickening show additional thickening of the mitral valve

thick tricuspid valve ( J:103391 )

• 8 of 24 (33.3%) of homozygotes display thickening of tricuspid valve thickening, with additional thickening of the mitral valve in 3 cases

double inlet heart left ventricle ( J:41682 )

• at E18.5, 4 of 16 homozygotes exhibit DILV

abnormal heart septum morphology ( J:103391 )

• at E13.5 to E18.5, homozygotes show a variable degree of hypoplasia of tissues deriving from the outflow tract ridges and the septal parts of the AV cushions

ostium primum atrial septal defect ( J:103391 )

• at E18.5, 1 of 24 (4.2%) of homozygotes display a large primum-type of atrial septal defect; the lower rim of atrial septum is still mesenchymal and has not fused with AV cushions

atrioventricular septal defect ( J:103391 )

• overall, 62.5% (15 of 24) of homozygotes aged E13.5 to 18.5 display defects related to the region of the AV canal and the ventricular inlet segment

complete atrioventricular septal defect ( J:103391 )

• 1 of 24 (4.2%) of homozygotes display a complete atrioventricular septal defect

perimembraneous ventricular septal defect ( J:103391 )

• 6 of 24 (25%) of homozygotes display overriding of tricuspid orifice via a perimembranous inlet VSD

inlet ventricular septal defect ( J:41682 , J:103391 )

• at E18.5, 15 of 16 homozygotes show ventricular septum defects (J:41682)

• 9 of 24 (37.5%) of homozygotes aged E13.5 to E18.5 show a perimembranous inlet VSD associated with overriding of the tricuspid orifice in 6 cases (J:103391)

• VSD is more closely related to the aortic orifice in cases with a posterior position of the latter (J:103391)

• in case of a deficient outflow tract septum, the VSD is committed to both arterial orifices (J:103391)

abnormal semilunar valve morphology ( J:41682 , J:103391 )

• at E18.5, the aortic and pulmonary orifices are both above the right ventricle; both exhibit valve leaflets that are patent (J:41682)

• 1 of 24 (4.2%) of homozygotes show thickening of the semilunar valve leaflets (J:103391)

heart valve hyperplasia ( J:103391 )

• in contrast to septal hypoplasia, E18.5 homozygotes show abnormalities of AV and semilunar valve differentiation

• mutant valve leaflets are hyperplastic and retain a thick and cushion-like appearance

• right-sided valves (tricuspid and pulmonary) are more frequently affected than left-sided valves (mitral and aortic)

abnormal heart ventricle outflow tract morphology ( J:103391 )

• dextroposition of the outflow tract results in a large-outlet VSD due to aberrant position of the outflow tract septum relative to the ventricular septum

thick aortic valve cusps ( J:103391 )

• 1 of 24 (4.2%) of homozygotes show thickening of the aortic valve leaflets

patent aortic valve ( J:41682 )

thick pulmonary valve cusps ( J:103391 )

• 2 of 24 (8.3%) of homozygotes show thickening of the leaflets of the pulmonary valve, with thickening of the aortic valve in one case

patent pulmonary valve ( J:41682 )

dilated heart right ventricle ( J:41682 , J:103391 )

• at E18.5, homozygotes exhibit an enlarged right ventricle (J:41682)

• at E15.5, the myocardium of the right ventricle appears spongier, probably due to ventricular dilatation (J:103391)

hearing/vestibular/ear

abnormal cochlea morphology ( J:41682 )

absent Rosenthal canal ( J:41682 )

abnormal scala vestibuli morphology ( J:41682 )

• at E18.5, all homozygotes show incomplete canalization of the scala vestibuli

• a wider space between the epithelial ridge and basilar membrane is observed

absent interdental cells ( J:41682 )

• the interdental cells overlying the spiral limbus appear undifferentiated

absent spiral limbus ( J:41682 )

• unlike wild-type mice, all homozygotes fail to form the spiral limbus in the basal cochlear turn by E18.5

homeostasis/metabolism

cyanosis ( J:41682 )

• one-third of homozygotes that are born live exhibit congenital cyanosis

increased urine protein level ( J:41682 )

endocrine/exocrine glands

ectopic adrenal gland ( J:41682 )

• at E18.5, 1 of 5 female homozygotes shows adrenal ectopia

testis hypoplasia ( J:41682 )

♂ • at E18.5, 1 of 5 males displays unilateral testicular hypoplasia with absence of an epididymis and vas deferens dysgenesis

ectopic testis ( J:41682 )

♂ • at E18.5, all male homozygotes exhibit testicular ectopia

immune system

abnormal macrophage physiology ( J:73681 )

• at E13.5 or later, homozygotes exhibit failure of macrophage invasion into ocular tissues, suggesting impaired removal of vitreous hyaline cells

reproductive system

testis hypoplasia ( J:41682 )

♂ • at E18.5, 1 of 5 males displays unilateral testicular hypoplasia with absence of an epididymis and vas deferens dysgenesis

ectopic testis ( J:41682 )

♂ • at E18.5, all male homozygotes exhibit testicular ectopia

abnormal uterine horn morphology ( J:41682 )

♀ • at E18.5, 2 of 5 female homozygotes display uterine horn ectopia by ventral displacement relative to the kidneys

respiratory system

atelectasis ( J:41682 )

• postnatally, all mutant lungs display collapsed terminal and respiratory bronchioles

dilated respiratory conducting tube ( J:41682 )

• postnatally, all mutant lungs exhibit dilated conducting airways

respiratory distress ( J:41682 )

• live-born homozygotes exhibit respiratory distress

skeleton

abnormal craniofacial bone morphology ( J:41682 )

• at E18.5, all homozygotes exhibit reduced cranial ossification of the frontal, interparietal, parietal and squamosal bones

abnormal neurocranium morphology ( J:41682 )

• at E18.5, most homozygotes display dysmorphic calvaria

large fontanelles ( J:41682 )

• at E18.5, all homozygotes display enlarged fontanelles

small frontal bone ( J:41682 )

• at E18.5, all homozygotes exhibit reduced frontal bones

small interparietal bone ( J:41682 )

• at E18.5, all homozygotes exhibit reduced interparietal bones

absent occipital bone ( J:41682 )

• at E18.5, all homozygotes show a nearly complete agenesis of the occipital bone

small parietal bone ( J:41682 )

• at E18.5, all homozygotes exhibit reduced parietal bones

absent alisphenoid bone ( J:41682 )

• at E18.5, all homozygotes show a nearly complete agenesis of the alisphenoid bone

absent pterygoid process ( J:41682 )

• at E18.5, homozygotes with cleft palate (23%) show absence of the pterygoid process of the basisphenoid bone

small temporal bone ( J:41682 )

• at E18.5, all homozygotes exhibit reduced temporal bones

abnormal mandible morphology ( J:41682 )

• at E18.5, the masseteric ridge is more prominent and anteriorly and dorsally displaced

absent mandibular angle ( J:41682 )

• at E18.5, all mutant mandibles lack an angle

small mandibular condyloid process ( J:41682 )

• at E18.5, the condyloid process is reduced to one-half of wild-type size

small mandibular coronoid process ( J:41682 )

• at E18.5, the coronoid process is reduced to one-half of wild-type size

short mandible ( J:41682 )

absent maxillary shelf ( J:41682 )

• at E18.5, homozygotes with cleft palate (23%) show absence of the palatine shelf

retrognathia ( J:41682 )

• at E18.5, most homozygotes display retrognathia

spina bifida occulta ( J:41682 )

• newborn homozygotes exhibit spina bifida occulta

• mutant neural arches form but fail to fuse at the midline of the neural tube

• typically, neural arch defects range from the 10th thoracic to the 5th caudal vertebra

abnormal humerus morphology ( J:41682 )

absent deltoid tuberosity ( J:41682 )

• all newborn homozygotes lack the deltoid tuberosity on the humerus

short radius ( J:41682 )

• all newborn homozygotes exhibit a shortened radius

small olecranon ( J:41682 )

• all newborn homozygotes exhibit a shortened ulna with a reduced olecranon process

short ulna ( J:41682 )

• all newborn homozygotes exhibit a shortened ulna with a reduced olecranon process

abnormal femur morphology ( J:41682 )

abnormal trochanter morphology ( J:41682 )

• all newborn homozygotes lack the third trochanter on the femur

abnormal clavicle morphology ( J:41682 )

• at E18.5, homozygotes show ventral curvature of the clavicles

abnormal sternum morphology ( J:41682 )

• at E18.5, 4 of 16 homozygotes display sternum abnormalities, including bifurcation, incomplete manubrium, and vestigial xiphoid process

abnormal xiphoid process morphology ( J:41682 )

• at E18.5, 4 of 16 homozygotes display a vestigial xiphoid process

abnormal rib morphology ( J:41682 )

• one-third of homozygotes exhibit wavy irregular ribs or fused ribs

rib fusion ( J:41682 )

• at E18.5, 2 of 16 homozygotes display rib fusions

abnormal thoracic cage shape ( J:41682 )

• at E18.5, 15 of 16 homozygotes exhibit rib barreling, resulting in a larger, more rounded pulmonary cavity

vision/eye

abnormal iris stroma morphology ( J:73681 )

• at E18.5, the mutant iris stroma is underdeveloped

absent Descemet membrane ( J:73681 )

• at E14.5, a Descemet's membrane fails to form

absent cornea endothelium ( J:73681 )

• at E14.5, no endothelium forms in cornea, limbus and trabecular meshworks

• in contrast, corneal epithelium morphology appears unaffected

decreased cornea thickness ( J:73681 )

• at E13.5-E14.5, the mutant cornea is abnormally thin

abnormal cornea stroma morphology ( J:73681 )

• at E14.5-E18.5, the central stroma adheres to the lens capsule

• at E18.5, reduced collagenous matrix accumulation is noted in the extracellular space between stromal keratocytes

decreased cornea stroma thickness ( J:41682 , J:73681 )

• at E18.5, all homozygotes display reduced corneal stroma thickness (~33% of wild-type) (J:41682)

• at E13.5-E14.5, the mutant corneal stroma is significantly thinner with fewer keratocytes than wild-type stroma (J:73681)

• intercellular spacing is reduced due to decreased ECM accumulation (collagen I, lumican, and keratocan) rather than impaired keratocyte proliferation or enhanced keratocyte apoptosis (J:73681)

abnormal cornea posterior stroma morphology ( J:73681 )

• at E18.5, cells at the posterior stroma fail to form a continuous endothelial cell layer

• no intercellular junctional complex or basal lamella-like structure is observed in the posterior cornea

fused cornea and lens ( J:73681 )

• at E13.5-E14.5, the mutant cornea fails to separate from the lens

absent eye anterior chamber ( J:73681 )

• at E14.5, an anterior chamber fails to form

abnormal eye posterior chamber morphology ( J:41682 )

• at E18.5, all homozygotes contain a hypercellular infusion of vascularized melanocytes, neuronal cells, and mesenchymal cells in the posterior eye chamber

persistence of hyaloid vascular system ( J:73681 )

• at E18.5, remnant capillaries are found between the stroma and lens capsule

abnormal retina neuronal layer morphology ( J:73681 )

• the mutant neural retina fails to laminate and undergo normal differentiation by E18.5

retina hyperplasia ( J:41682 )

• at E18.5, all homozygotes show hyperplasia of both the inner and outer neuroblastic layers of the retina

vitreous body deposition ( J:73681 )

• at E18.5, a huge cell mass of hyalocytes and blood cells accumulates in the vitreous

nervous system

spina bifida occulta ( J:41682 )

• newborn homozygotes exhibit spina bifida occulta

• mutant neural arches form but fail to fuse at the midline of the neural tube

• typically, neural arch defects range from the 10th thoracic to the 5th caudal vertebra

abnormal cochlear ganglion morphology ( J:41682 )

• at E18.5, the mutant spiral ganglion abnormally lies close to the sensory epithelium due to absence of the spiral limbus and Rosenthal's canal

muscle

abnormal myocardium layer morphology ( J:41682 , J:103391 )

• at E18.5, the mutant myocardium is hypercellular and less trabeculated (J:41682)

• at E18.5, some homozygotes display normal myocardialization of outflow tract cushions; others exhibit absence of myocardialization, with only a small fibrous ridge below the semilunar valves (J:103391)

trabecula carnea hypoplasia ( J:41682 )

limbs/digits/tail

abnormal limb morphology ( J:41682 )

• newborn homozygotes display limb laxity; both fore- and hindlimbs are rotated and extend toward the midline

abnormal humerus morphology ( J:41682 )

absent deltoid tuberosity ( J:41682 )

• all newborn homozygotes lack the deltoid tuberosity on the humerus

short radius ( J:41682 )

• all newborn homozygotes exhibit a shortened radius

small olecranon ( J:41682 )

• all newborn homozygotes exhibit a shortened ulna with a reduced olecranon process

short ulna ( J:41682 )

• all newborn homozygotes exhibit a shortened ulna with a reduced olecranon process

abnormal femur morphology ( J:41682 )

abnormal trochanter morphology ( J:41682 )

• all newborn homozygotes lack the third trochanter on the femur

growth/size/body

absent maxillary shelf ( J:41682 )

• at E18.5, homozygotes with cleft palate (23%) show absence of the palatine shelf

cleft secondary palate ( J:41682 )

• at E18.5, 23% of homozygotes display an extensive anteroposterior cleft of the secondary palate, leaving the nasal septa exposed and extending into the soft palate

• no primary palate cleft or cleft lip was ever observed

failure of palatal shelf elevation ( J:41682 )

• observed at day E18.5, mice show a failure of the palatal shelves to elevate into a horizontal orientation for the process of apposition and fusion

decreased body weight ( J:41682 )

• E18.5 homozygotes delivered by Cesarean section show a 12% reduction in birth weight

craniofacial

abnormal craniofacial bone morphology ( J:41682 )

• at E18.5, all homozygotes exhibit reduced cranial ossification of the frontal, interparietal, parietal and squamosal bones

abnormal neurocranium morphology ( J:41682 )

• at E18.5, most homozygotes display dysmorphic calvaria

large fontanelles ( J:41682 )

• at E18.5, all homozygotes display enlarged fontanelles

small frontal bone ( J:41682 )

• at E18.5, all homozygotes exhibit reduced frontal bones

small interparietal bone ( J:41682 )

• at E18.5, all homozygotes exhibit reduced interparietal bones

absent occipital bone ( J:41682 )

• at E18.5, all homozygotes show a nearly complete agenesis of the occipital bone

small parietal bone ( J:41682 )

• at E18.5, all homozygotes exhibit reduced parietal bones

absent alisphenoid bone ( J:41682 )

• at E18.5, all homozygotes show a nearly complete agenesis of the alisphenoid bone

absent pterygoid process ( J:41682 )

• at E18.5, homozygotes with cleft palate (23%) show absence of the pterygoid process of the basisphenoid bone

small temporal bone ( J:41682 )

• at E18.5, all homozygotes exhibit reduced temporal bones

abnormal mandible morphology ( J:41682 )

• at E18.5, the masseteric ridge is more prominent and anteriorly and dorsally displaced

absent mandibular angle ( J:41682 )

• at E18.5, all mutant mandibles lack an angle

small mandibular condyloid process ( J:41682 )

• at E18.5, the condyloid process is reduced to one-half of wild-type size

small mandibular coronoid process ( J:41682 )

• at E18.5, the coronoid process is reduced to one-half of wild-type size

short mandible ( J:41682 )

absent maxillary shelf ( J:41682 )

• at E18.5, homozygotes with cleft palate (23%) show absence of the palatine shelf

retrognathia ( J:41682 )

• at E18.5, most homozygotes display retrognathia

cleft secondary palate ( J:41682 )

• at E18.5, 23% of homozygotes display an extensive anteroposterior cleft of the secondary palate, leaving the nasal septa exposed and extending into the soft palate

• no primary palate cleft or cleft lip was ever observed

failure of palatal shelf elevation ( J:41682 )

• observed at day E18.5, mice show a failure of the palatal shelves to elevate into a horizontal orientation for the process of apposition and fusion

renal/urinary system

increased urine protein level ( J:41682 )

abnormal kidney morphology ( J:41682 )

• following tubulogenesis, female homozygotes show renal dysplastic changes, including renal tubule dilatation, degeneration of the tubular epithelium, proteinuria, and enlargement of the renal pelvis

abnormal renal tubule epithelium morphology ( J:41682 )

• when kidneys form in females, tubulogenesis is followed by degeneration of the tubular epithelium

hydronephrosis ( J:41682 )

• at E18.5, 3 of 10 homozygotes show a dilated renal pelvis

dilated renal tubule ( J:41682 )

• when kidneys form in females, tubulogenesis is followed by progressive tubule dilatation

absent kidney ( J:41682 )

• at E18.5, 1 of 5 homozygotes (females only) shows renal agenesis

digestive/alimentary system

absent maxillary shelf ( J:41682 )

• at E18.5, homozygotes with cleft palate (23%) show absence of the palatine shelf

cleft secondary palate ( J:41682 )

• at E18.5, 23% of homozygotes display an extensive anteroposterior cleft of the secondary palate, leaving the nasal septa exposed and extending into the soft palate

• no primary palate cleft or cleft lip was ever observed

failure of palatal shelf elevation ( J:41682 )

• observed at day E18.5, mice show a failure of the palatal shelves to elevate into a horizontal orientation for the process of apposition and fusion

embryo

spina bifida occulta ( J:41682 )

• newborn homozygotes exhibit spina bifida occulta

• mutant neural arches form but fail to fuse at the midline of the neural tube

• typically, neural arch defects range from the 10th thoracic to the 5th caudal vertebra

hematopoietic system

abnormal macrophage physiology ( J:73681 )

• at E13.5 or later, homozygotes exhibit failure of macrophage invasion into ocular tissues, suggesting impaired removal of vitreous hyaline cells

Genotype
MGI:3848993

hm3

• Allelic Composition: Tgfb2^tm1Doe/Tgfb2^tm1Doe
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

vision/eye

primary vitreous hyperplasia ( J:149526 )

• by E13.5 mice display increased cell density in the primary vitreous

• at E18.5 and P0 mice display primary vitreous hyperplasia

Genotype
MGI:5008270

ht4

• Allelic Composition: Tgfb2^tm1Doe/Tgfb2⁺
• Genetic Background: involves: 129P2/OlaHsd

digestive/alimentary system

decreased enterocyte apoptosis ( J:76342 )

• mice exhibit reduced enterocyte apoptosis in the small intestine compared with wild-type mice

• however, enterocyte apoptosis in the colon is normal

abnormal small intestinal villus morphology ( J:76342 )

• villus length is increased compared to in wild-type mice

cellular

decreased enterocyte apoptosis ( J:76342 )

• mice exhibit reduced enterocyte apoptosis in the small intestine compared with wild-type mice

• however, enterocyte apoptosis in the colon is normal

Genotype
MGI:2668214

ht5

• Allelic Composition: Tgfb2^tm1Doe/Tgfb2⁺
• Genetic Background: involves: 129P2/OlaHsd * Black Swiss

endocrine/exocrine glands

abnormal bulbourethral gland morphology ( J:78547 )

♂ • adult male heterozygotes exhibit Cowper's gland hyperplasia, local atrophy, ductal transformation and cystic dilation

bulbourethral gland cyst ( J:78547 )

♂ • heterozygores are viable and fertile; however, some male heterozygotes develop palpable cysts in the perineal/scrotal region (9 cysts in 21 males; 1-2 cysts per animal)

♂ • young (2-4-mo-old) males have small, externally non-visible cysts

♂ • older (>7-mo-old) males exhibit large, fluid-filled cysts located deep to the pelvic floor, dorso-laterally of the ischiocavernosus and bulbocavernosus muscles (Cowper's syringoceles), suggesting impaired epithelial-stromal interactions

♂ • the cellular lining of the cyst wall exhibits heterogeneity of the epithelial lining ranging from single layered squamous epithelium to multilayered glandular structures covering papillary folds

♂ • severely hyperplastic cells from the cyst wall exhibit extreme overload of polymorphic secretory material; stratified epithelium from the cyst wall is devoid of any signs of secretion

bulbourethral gland hyperplasia ( J:78547 )

♂ • adult male heterozygotes exhibit glandular hyperplasia of Cowper's gland with thickening of the surrounding muscular capsule

♂ • the hyperplastic glandular epithelium is multilayered with large foamy or vacuolated cells and irregular nuclear structure and position

prostate gland anterior lobe hyperplasia ( J:78547 )

♂ • male heterozygotes exhibit coagulating gland hyperplasia

abnormal bulbourethral gland physiology ( J:78547 )

♂ • hyperplastic Cowper's glands exhibit an ~80% reduction in apoptotic cell death relative to wild-type glands

reproductive system

abnormal bulbourethral gland morphology ( J:78547 )

♂ • adult male heterozygotes exhibit Cowper's gland hyperplasia, local atrophy, ductal transformation and cystic dilation

bulbourethral gland cyst ( J:78547 )

♂ • heterozygores are viable and fertile; however, some male heterozygotes develop palpable cysts in the perineal/scrotal region (9 cysts in 21 males; 1-2 cysts per animal)

♂ • young (2-4-mo-old) males have small, externally non-visible cysts

♂ • older (>7-mo-old) males exhibit large, fluid-filled cysts located deep to the pelvic floor, dorso-laterally of the ischiocavernosus and bulbocavernosus muscles (Cowper's syringoceles), suggesting impaired epithelial-stromal interactions

♂ • the cellular lining of the cyst wall exhibits heterogeneity of the epithelial lining ranging from single layered squamous epithelium to multilayered glandular structures covering papillary folds

♂ • severely hyperplastic cells from the cyst wall exhibit extreme overload of polymorphic secretory material; stratified epithelium from the cyst wall is devoid of any signs of secretion

bulbourethral gland hyperplasia ( J:78547 )

♂ • adult male heterozygotes exhibit glandular hyperplasia of Cowper's gland with thickening of the surrounding muscular capsule

♂ • the hyperplastic glandular epithelium is multilayered with large foamy or vacuolated cells and irregular nuclear structure and position

prostate gland anterior lobe hyperplasia ( J:78547 )

♂ • male heterozygotes exhibit coagulating gland hyperplasia

abnormal bulbourethral gland physiology ( J:78547 )

♂ • hyperplastic Cowper's glands exhibit an ~80% reduction in apoptotic cell death relative to wild-type glands

abnormal spermatogenesis ( J:78547 )

♂ • male heterozygotes show a reduced yield of spermatogenesis

oligozoospermia ( J:78547 )

♂

teratozoospermia ( J:78547 )

♂ • male heterozygotes display malformed spermatozoa

cellular

oligozoospermia ( J:78547 )

♂

teratozoospermia ( J:78547 )

♂ • male heterozygotes display malformed spermatozoa

growth/size/body

bulbourethral gland cyst ( J:78547 )

♂ • heterozygores are viable and fertile; however, some male heterozygotes develop palpable cysts in the perineal/scrotal region (9 cysts in 21 males; 1-2 cysts per animal)

♂ • young (2-4-mo-old) males have small, externally non-visible cysts

♂ • older (>7-mo-old) males exhibit large, fluid-filled cysts located deep to the pelvic floor, dorso-laterally of the ischiocavernosus and bulbocavernosus muscles (Cowper's syringoceles), suggesting impaired epithelial-stromal interactions

♂ • the cellular lining of the cyst wall exhibits heterogeneity of the epithelial lining ranging from single layered squamous epithelium to multilayered glandular structures covering papillary folds

♂ • severely hyperplastic cells from the cyst wall exhibit extreme overload of polymorphic secretory material; stratified epithelium from the cyst wall is devoid of any signs of secretion

Genotype
MGI:3758329

ht6

• Allelic Composition: Tgfb2^tm1Doe/Tgfb2⁺
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * Black Swiss * C57BL/6J

nervous system

decreased dopaminergic neuron number ( J:108007 )

• heterozygotes have 12% fewer dopaminergic neurons than wild-type littermates at 6 weeks of age; no further reduction is seen at 6 months of age

homeostasis/metabolism

decreased dopamine level ( J:108007 )

• in aged (6-month old) mice, dopamine levels are only 70% of wild-type levels in the striatum; at 6 months, the dihydroxyphenyacetic acid/dopamine ratio (DOPAC/dopamine) is significantly increased relative to wild-type

Genotype
MGI:5444484

ht7

• Allelic Composition: Tgfb2^tm1Doe/Tgfb2⁺
• Genetic Background: STOCK Tgfb2^tm1Doe/J

cardiovascular system

abnormal aorta wall morphology ( J:188799 )

• elastic fiber fragmentation and greater collagen deposition within the medial compartment of the aortic wall is increased compared to wild-type mice

dilated aorta bulb ( J:188799 )

• by 8 months of age, heterozygotes show dilation of the aortic annulus and root

• however, dimensions of the more distal ascending aorta are normal

aortic aneurysm ( J:188799 )

• aortic root aneurysm

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Loeys-Dietz syndrome		DOID:0050466		J:188799

Genotype
MGI:4360749

cn8

• Allelic Composition: Ext1^tm1Yama/Ext1⁺; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺; Tgfb2^tm1Doe/Tgfb2⁺
• Genetic Background: B6.Cg-Tgfb2^tm1Doe H2az2^{Tg(Wnt1-cre)11Rth} Ext1^tm1Yama

Thin cornea and iridocorneal dysgenesis in Ext1^tm1Yama/Ext1⁺ H2az2^{Tg(Wnt1-cre)11Rth}/0 Tgfb2^tm1Doe/Tgfb2⁺ mice

mortality/aging

mortality/aging ( J:152572 )

N • mice survive into adulthood

vision/eye

abnormal aqueous drainage system morphology ( J:152572 )

• mice exhibit defects in components of the aqueous drainage system

• however, the iridocorneal angle is normal

abnormal canal of Schlemm morphology ( J:152572 )

abnormal trabecular meshwork morphology ( J:152572 )

• the trabecular beam contains fewer cells than in wild-type mice

ocular hypertension ( J:152572 )

• mice exhibit ocular hypertension unlike single heterozygotes

Genotype
MGI:5008265

cx9

• Allelic Composition: Tgfb2^tm1Doe/Tgfb2⁺; Tgfb3^tm1Doe/Tgfb3^tm1Doe
• Genetic Background: involves: 129P2/OlaHsd

limbs/digits/tail

limbs/digits/tail phenotype ( J:76541 )

N • mice exhibit normal apoptosis of interdigital webbing

vision/eye

vision/eye phenotype ( J:105113 )

N • mice exhibit normal retinal morphology

Genotype
MGI:5008266

cx10

• Allelic Composition: Tgfb2^tm1Doe/Tgfb2^tm1Doe; Tgfb3^tm1Doe/Tgfb3^tm1Doe
• Genetic Background: involves: 129P2/OlaHsd

vision/eye

abnormal retina apoptosis ( J:105113 )

• retinal cell death is reduced compared to in wild-type mice

abnormal cornea morphology ( J:105113 )

• cornea appear to exfoliate unlike in wild-type mice

decreased cornea thickness ( J:105113 )

decreased cornea stroma thickness ( J:105113 )

abnormal eye posterior chamber morphology ( J:105113 )

• mice exhibit vascularized accumulation of cells in the posterior chamber of the eye unlike in wild-type mice

abnormal lens epithelium morphology ( J:105113 )

• lens epithelium thickness is decreased compared to in wild-type mice

abnormal retina neuronal layer morphology ( J:105113 )

• mice exhibit thickened neural retina compared with wild-type mice

• the neural retina is consistently detached from the pigment epithelium unlike in wild-type mice

• however, the outer retina and optic fiber layers are of normal thickness

abnormal retina inner nuclear layer morphology ( J:105113 )

• thickened

limbs/digits/tail

interdigital webbing ( J:76541 )

• at E15.5

abnormal digit development ( J:76541 )

• at E13.5 and E14.5, mice lack mesenchymal indentation between future digits unlike wild-type mice

abnormal interdigital cell death ( J:76541 )

• at E13.5 and E14.5, mice exhibit decreased apoptosis in the interdigital zone compared to in wild-type mice

skeleton

abnormal cartilage development ( J:76541 )

• at E15.5, chondrogenesis in the digits is accelerated compared to in wild-type mice

abnormal chondrocyte morphology ( J:76541 )

• large hypertrophied chondrocytes with huge nuclei

cellular

abnormal interdigital cell death ( J:76541 )

• at E13.5 and E14.5, mice exhibit decreased apoptosis in the interdigital zone compared to in wild-type mice

abnormal retina apoptosis ( J:105113 )

• retinal cell death is reduced compared to in wild-type mice

Genotype
MGI:5008267

cx11

• Allelic Composition: Tgfb2^tm1Doe/Tgfb2^tm1Doe; Tgfb3^tm1Doe/Tgfb3⁺
• Genetic Background: involves: 129P2/OlaHsd

vision/eye

decreased retina apoptosis ( J:105113 )

• retinal cell death is reduced compared to in wild-type mice

abnormal cornea morphology ( J:105113 )

• with detached areas

decreased cornea stroma thickness ( J:105113 )

abnormal eye posterior chamber morphology ( J:105113 )

• mice exhibit vascularized accumulation of cells in the posterior chamber of the eye unlike in wild-type mice

abnormal lens epithelium morphology ( J:105113 )

• lens epithelium thickness is decreased compared to in wild-type mice

abnormal retina neuronal layer morphology ( J:105113 )

• mice exhibit thickened neural retina compared with wild-type mice

• the neural retina is consistently detached from the pigment epithelium unlike in wild-type mice

• however, the outer retina and optic fiber layers are of normal thickness

abnormal retina inner nuclear layer morphology ( J:105113 )

• thickened

limbs/digits/tail

abnormal interdigital cell death ( J:76541 )

• at E13.5, mice exhibit decreased apoptosis in the interdigital zone compared to in wild-type mice

interdigital webbing ( J:76541 )

• at E15.5

skeleton

abnormal cartilage development ( J:76541 )

• at E15.5, chondrogenesis in the digits is accelerated compared to in wild-type mice

cellular

abnormal interdigital cell death ( J:76541 )

• at E13.5, mice exhibit decreased apoptosis in the interdigital zone compared to in wild-type mice

decreased retina apoptosis ( J:105113 )

• retinal cell death is reduced compared to in wild-type mice

Genotype
MGI:5008269

cx12

• Allelic Composition: Tgfb2^tm1Doe/Tgfb2⁺; Tgfb3^tm1Doe/Tgfb3⁺
• Genetic Background: involves: 129P2/OlaHsd

digestive/alimentary system

decreased enterocyte apoptosis ( J:76342 )

• mice exhibit reduced enterocyte apoptosis in the small intestine compared with wild-type mice

• however, enterocyte apoptosis in the colon is normal

abnormal small intestinal villus morphology ( J:76342 )

• villus length is increased compared to in wild-type mice

cellular

decreased enterocyte apoptosis ( J:76342 )

• mice exhibit reduced enterocyte apoptosis in the small intestine compared with wild-type mice

• however, enterocyte apoptosis in the colon is normal

Genotype
MGI:5444488

cx13

• Allelic Composition: Fbn1^tm1Hcd/Fbn1⁺; Tgfb2^tm1Doe/Tgfb2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J

cardiovascular system

abnormal aorta wall morphology ( J:188799 )

• elastic fiber fragmentation and greater collagen deposition within the medial compartment of the aortic wall is increased compared to either single heterozygote

dilated aorta bulb ( J:188799 )

• mutants show an increase in aortic root dimension at 2 and 4 months of age compared to either single heterozygote

• aortic dilatation is specific to the aortic root

aortic aneurysm ( J:188799 )

• aortic root aneurysm

growth/size/body

growth/size/body region phenotype ( J:188799 )

N • mutants exhibit normal body size and growth

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Loeys-Dietz syndrome		DOID:0050466		J:188799

Genotype
MGI:3848994

cx14

• Allelic Composition: Cdkn2a^tm1(GFP)Cjs/Cdkn2a^tm1(GFP)Cjs; Tgfb2^tm1Doe/Tgfb2^tm1Doe
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6

vision/eye

primary vitreous hyperplasia ( J:149526 )

• seen at E15.5

Genotype
MGI:3848995

cx15

• Allelic Composition: Cdkn2a^tm1(GFP)Cjs/Cdkn2a^tm1(GFP)Cjs; Tgfb2^tm1Doe/Tgfb2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6

vision/eye

primary vitreous hyperplasia ( J:149526 )

• seen at E15.5

Genotype
MGI:3848999

cx16

• Allelic Composition: Cdkn2a^tm1Cjs/Cdkn2a⁺; Tgfb2^tm1Doe/Tgfb2^tm1Doe
• Genetic Background: involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6

vision/eye

primary vitreous hyperplasia ( J:149526 )

Genotype
MGI:3848997

cx17

• Allelic Composition: Cdkn2a^tm1Sxs/Cdkn2a⁺; Tgfb2^tm1Doe/Tgfb2^tm1Doe
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * C57BL/6

vision/eye

primary vitreous hyperplasia ( J:149526 )

• seen at E13.5