All Phenotypes Smad3<tm1Cxd> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Smad3^tm1Cxd/Smad3^tm1Cxd	B6.129S6-Smad3^tm1Cxd	MGI:3760086
hm2	Smad3^tm1Cxd/Smad3^tm1Cxd	either: (involves: 129S6/SvEvTac * C57BL/6) or (involves: 129S6/SvEvTac * NIH Black Swiss)	MGI:2182598
hm3	Smad3^tm1Cxd/Smad3^tm1Cxd	involves: 129S6/SvEvTac	MGI:3760091
hm4	Smad3^tm1Cxd/Smad3^tm1Cxd	involves: 129S6/SvEvTac * C57BL/6	MGI:3851999
cn5	Smad2^tm1.1Epb/Smad2^tm1.1Epb Smad3^tm1Cxd/Smad3^tm1Cxd Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺	involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * DBA * SJL	MGI:3703883
cx6	Smad2^tm1Cxd/Smad2⁺ Smad3^tm1Cxd/Smad3⁺	involves: 129S6/SvEvTac * C57BL/6	MGI:3758897
cx7	Smad2^tm1Cxd/Smad2⁺ Smad3^tm1Cxd/Smad3⁺	involves: 129S6/SvEvTac * NIH Black Swiss	MGI:3758892
cx8	Smad2^tm1.1Epb/Smad2^tm1.1Epb Smad3^tm1Cxd/Smad3^tm1Cxd	involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * SJL	MGI:3703878

Allelic Composition	Smad3^tm1Cxd/Smad3^tm1Cxd
Genetic Background	B6.129S6-Smad3^tm1Cxd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad3^tm1Cxd mutation (0 available); any Smad3 mutation (18 available)

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

cardiovascular system

abnormal vascular wound healing ( J:108527 )

• neointimal hyperplasia is enhanced in response to arterial injury compared to wild-type

• intima contains more proliferating smooth muscle cells with less collagen deposition than in wild-type

• growth of intimal smooth muscle cells (SMC) is only weakly inhibited by TGF-beta in vitro compared to wild-type, however chemotaxis of SMC towards TGF-beta is normal

homeostasis/metabolism

abnormal vascular wound healing ( J:108527 )

• neointimal hyperplasia is enhanced in response to arterial injury compared to wild-type

• intima contains more proliferating smooth muscle cells with less collagen deposition than in wild-type

• growth of intimal smooth muscle cells (SMC) is only weakly inhibited by TGF-beta in vitro compared to wild-type, however chemotaxis of SMC towards TGF-beta is normal

decreased susceptibility to injury ( J:102084 )

• at 14 days after unilateral ureteral obstruction (UUO), the mutant obstructed kidney shows attenuated scar formation, and decreased renal interstitial fibrosis, inflammation and apoptosis relative to the wild-type obstructed kidney

renal/urinary system

renal/urinary system phenotype ( J:102084 )

N	• prior to unilateral ureteral obstruction (UUO), 10 -12 week-old mutant mice exhibit histologically normal kidneys and normal serum blood urea nitrogen (BUN) and creatinine levels relative to wild-type controls

decreased renal tubule apoptosis ( J:102084 )

• at 14 days after UUO, the number of TUNEL-positive tubular apoptotic cells is significantly reduced in the obstructed mutant kidney relative to that in wild-type controls

tubulointerstitial nephritis ( J:102084 )

• at 14 days after UUO, the numbers of F4/80-positive interstitial macrophages, and CD4-positive and CD8-positive interstitial cells are significantly reduced in the obstructed mutant kidney relative to that in wild-type controls

renal interstitial fibrosis ( J:102084 )

• at 14 days after UUO, renal interstitial fibrosis is significantly attenuated in the obstructed mutant kidney relative to that in wild-type controls, as shown by Aniline-blue or Sirius red staining

• at 14 days after UUO, deposition of type I and type III collagens and the number of of alpha-SMA-positive interstitial myofibroblasts are significantly reduced in the obstructed mutant kidney relative to that in wild-type controls

immune system

tubulointerstitial nephritis ( J:102084 )

cellular

decreased renal tubule apoptosis ( J:102084 )

• at 14 days after UUO, the number of TUNEL-positive tubular apoptotic cells is significantly reduced in the obstructed mutant kidney relative to that in wild-type controls

Allelic Composition	Smad3^tm1Cxd/Smad3^tm1Cxd
Genetic Background	either: (involves: 129S6/SvEvTac * C57BL/6) or (involves: 129S6/SvEvTac * NIH Black Swiss)

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad3^tm1Cxd mutation (0 available); any Smad3 mutation (18 available)

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

mortality/aging

premature death ( J:53510 )

• the 70% of mice that suffer from growth retardation and develop a wasting syndrome, typically die between 1 and 3 months of age

• remaining 30% die between 3 and 8 months of age with a similar wasting syndrome

growth/size/body

decreased body size ( J:53510 )

• 70% are smaller than wild-type prior to weaning

immune system

impaired neutrophil chemotaxis ( J:53510 )

• neutrophils show impaired chemotaxis to TGF-beta

abnormal thymus involution ( J:53510 )

• symptomatic mutants have an involuted thymus

abnormal T cell physiology ( J:53510 )

• T cells invade normal regions of B cell development and germinal center formation in lymph nodes

abnormal T cell activation ( J:53510 )

• lymph node T cells from enlarged submandibular and mesenteric lymph nodes exhibit an activated phenotype with an increased number of CD62L cells

abnormal immune system morphology ( J:53510 )

• multifocal formation of pyogenic abscesses, which are most often periorbital, periodontal, and within the wall of the stomach and the intestine

thymus hypoplasia ( J:53510 )

• symptomatic mutants show a reduction in the cellularity of the thymus

increased leukocyte cell number ( J:53510 )

• absolute increase in white blood cell counts

increased neutrophil cell number ( J:53510 )

• increased numbers of circulating neutrophils

increased monocyte cell number ( J:53510 )

• increased numbers of circulating monocytes

small spleen ( J:53510 )

• symptomatic mutants have a small spleen

spleen hypoplasia ( J:53510 )

• symptomatic mutants show a reduction in the cellularity of the spleen

enlarged mesenteric lymph nodes ( J:53510 )

enlarged lymph nodes ( J:53510 )

• symptomatic mutants have enlarged lymph nodes

• mediastinal, mandibular and mesenteric lymph nodes are enlarged in the majority of mutants; nodes display lymphoid hyperplasia, with extensive proliferation of T cells and an accumulation of plasma cells, effacing the normal node architecture

increased inflammatory response ( J:53510 )

• inflammatory lesions in many organs, including the nasal mucosa, stomach, pancreas, colon and small intestine

colitis ( J:53510 )

• inflammatory lesions in the colon

small intestinal inflammation ( J:53510 )

stomach inflammation ( J:53510 )

pancreas inflammation ( J:53510 )

hematopoietic system

impaired neutrophil chemotaxis ( J:53510 )

• neutrophils show impaired chemotaxis to TGF-beta

thymus hypoplasia ( J:53510 )

• symptomatic mutants show a reduction in the cellularity of the thymus

abnormal thymus involution ( J:53510 )

• symptomatic mutants have an involuted thymus

extramedullary hematopoiesis ( J:53510 )

• commonly see extramedullary hematopoiesis within the liver and spleen

increased leukocyte cell number ( J:53510 )

• absolute increase in white blood cell counts

increased neutrophil cell number ( J:53510 )

• increased numbers of circulating neutrophils

increased monocyte cell number ( J:53510 )

• increased numbers of circulating monocytes

small spleen ( J:53510 )

• symptomatic mutants have a small spleen

spleen hypoplasia ( J:53510 )

• symptomatic mutants show a reduction in the cellularity of the spleen

abnormal T cell physiology ( J:53510 )

• T cells invade normal regions of B cell development and germinal center formation in lymph nodes

abnormal T cell activation ( J:53510 )

• lymph node T cells from enlarged submandibular and mesenteric lymph nodes exhibit an activated phenotype with an increased number of CD62L cells

digestive/alimentary system

increased intestinal adenocarcinoma incidence ( J:53510 )

• rare (1 in 13 mice) development of colonic adenocardinomas in mice >6 months

colitis ( J:53510 )

• inflammatory lesions in the colon

small intestinal inflammation ( J:53510 )

stomach inflammation ( J:53510 )

endocrine/exocrine glands

thymus hypoplasia ( J:53510 )

• symptomatic mutants show a reduction in the cellularity of the thymus

abnormal thymus involution ( J:53510 )

• symptomatic mutants have an involuted thymus

pancreas inflammation ( J:53510 )

skeleton

kyphosis ( J:53510 )

• symptomatic mutants have a kyphotic posture

neoplasm

increased intestinal adenocarcinoma incidence ( J:53510 )

• rare (1 in 13 mice) development of colonic adenocardinomas in mice >6 months

cellular

impaired neutrophil chemotaxis ( J:53510 )

• neutrophils show impaired chemotaxis to TGF-beta

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

Skeletal defects in 7 month old Smad3^tm1Cxd/Smad3^tm1Cxd mice

skeleton

abnormal tarsal bone morphology ( J:68792 )

• about 30% of P1 mutants exhibit abnormal formation of tarsal bones

abnormal rib morphology ( J:68792 )

• ribs are distorted due to abnormal ossification

kyphosis ( J:68792 )

kyphoscoliosis ( J:68792 )

decreased bone mineral density ( J:68792 )

• decrease in bone density except in areas where osteophytes form

abnormal cartilage morphology ( J:68792 )

• P40 mutants show decreased proteoglycan content in articular cartilage and growth plates

abnormal chondrocyte morphology ( J:68792 )

• enhancement of terminal differentiation of epiphyseal growth plate chondrocytes shortly after weaning

abnormal joint morphology ( J:68792 )

• knee joints are enlarged due to osteophytes that develop at the joint margins and within the joint space; osteophytes are also found in sternum and vertebral bone joints

abnormal articular cartilage morphology ( J:68792 )

• synovial joint formation is normal, however mutants exhibit progressive articular cartilage degeneration

• the articular surface of joints with mild degeneration is covered with abnormally differentiated chondrocytes instead of a thin layer of resting chondrocytes

abnormal synovial joint capsule morphology ( J:68792 )

• surface fibrillation (vertical cleft development) and osteophytes with varying sizes are seen in synovial cavities of most 6 month old mutants; osteophytes contain both chondrocytes and osteoblasts in the outgrowth of endochondral tissues

calcified joint ( J:68792 )

• abnormal calcification of the synovial joints is seen in mutants over 6 months of age

abnormal epiphyseal plate morphology ( J:68792 )

• growth plates of P21 or older mutants contain fewer proliferating chondrocytes than controls

increased width of hypertrophic chondrocyte zone ( J:68792 )

• gradual increase in the height of the hypertrophic zone is seen in some 3-4 week old mutants and becomes more pronounced at 6-8 weeks of age

abnormal skeleton physiology ( J:68792 )

• bone rudiments from E17.5 metatarsals exhibit a diminished response to TGF-beta1 inhibition and do not show repression of hypertrophic zone expansion as is seen in controls

osteoarthritis ( J:68792 )

• progressive loss of articular cartilage leading to the development of degenerative joint disease

• formation of large osteophytes in joints

digestive/alimentary system

abnormal intestine morphology ( J:75703 )

• 7%-10% of mice die from intestinal abscesses by 3 months of age

immune system

abnormal leukocyte physiology ( J:59673 )

• monocytes show a selectively blunted chemotatic response to TGF-beta

decreased B cell apoptosis ( J:140567 )

• bone marrow-derived, IL-7- dependent pro-B lymphocytes fail to exhibit a TGFbeta induced increased in apoptosis following a 24 or 48 hour treatment

osteoarthritis ( J:68792 )

• progressive loss of articular cartilage leading to the development of degenerative joint disease

• formation of large osteophytes in joints

endocrine/exocrine glands

decreased primary ovarian follicle number ( J:75703 )

• at P2, the number of primary follicles per ovary is significantly lower than that in wild-type ovaries

• however, the number of healthy primary follicles is not significantly different at P7 or P18

increased primordial ovarian follicle number ( J:75703 )

• at P7, the number of primordial follicles per ovary is significantly higher than that in wild-type ovaries

• by P90, ovaries contain 2.7-fold more primordial follicles than wild-type ovaries

• at P18, ovaries contain ~61% more primordial follicles than wild-type ovaries

• however, no significant change in seen at P2, indicating a normal size of primordial follicle pool at birth

decreased secondary ovarian follicle number ( J:75703 )

• at P7, ovaries contain significantly fewer preantral follicles than wild-type ovaries

• at P18, ovaries contain 40% fewer preantral and antral follicles than wild-type ovaries

• by P90, ovaries contain 3-fold fewer preantral and antral follicles than wild-type ovaries

decreased tertiary ovarian follicle number ( J:75703 )

• at P7, ovaries contain significantly fewer preantral and antral follicles than wild-type ovaries

• at P18, ovaries contain 40% fewer preantral and antral follicles than wild-type ovaries

• by P90, ovaries contain 3-fold fewer preantral and antral follicles than wild-type ovaries

impaired ovarian folliculogenesis ( J:75703 )

• ovarian follicular development is impaired during adult life, as ovaries isolated at P7-P90 contain higher numbers of primordial follicles and lower numbers of large preantral and antral follicles than wild-type ovaries

growth/size/body

decreased body size ( J:75703 )

• mice are significantly smaller than wild-type and heterozygous controls

decreased body weight ( J:75703 )

• at P2, P7, P18 and P90, body weight is significantly lower than that in wild-type controls

homeostasis/metabolism

enhanced wound healing ( J:59673 )

• mutants show accelerated cutaneous wound healing compared with wild-type, characterized by an increased rate of re-epithelialization and reduced local infiltration of monocytes

decreased susceptibility to injury ( J:118474 )

• mutants exhibit protection against tubulointerstitial fibrosis following unilateral ureteral obstruction as evidenced by blocking of the epithelial-mesenchymal transition and abrogation of monocyte influx and collagen accumulation

mortality/aging

premature death ( J:75703 )

• 7%-10% of mice die from intestinal abscesses by 3 months of age

renal/urinary system

abnormal kidney epithelium morphology ( J:118474 )

• cultured primary renal tubular epithelial cells do not respond to TGF-beta1 and do not undergo the epithelial-to-mesenchymal transition (EMT) as wild-type cells and retain features of an epithelial monolayer

• cyclic mechanical stretching of mutant renal tubular epithelial cells in culture does not elicit EMT as in wild-type

• mutant epithelial cells show no phenotypic change when cocultured with monocytes unlike wild-type which show a fibroblastic appearance (exhibit EMT)

behavior/neurological

abnormal locomotor behavior ( J:68792 )

• mutants show progressive loss of movement due to degenerative joint disease

reproductive system

decreased primary ovarian follicle number ( J:75703 )

• however, the number of healthy primary follicles is not significantly different at P7 or P18

• at P2, the number of primary follicles per ovary is significantly lower than that in wild-type ovaries

increased primordial ovarian follicle number ( J:75703 )

• at P7, the number of primordial follicles per ovary is significantly higher than that in wild-type ovaries

• by P90, ovaries contain 2.7-fold more primordial follicles than wild-type ovaries

• at P18, ovaries contain ~61% more primordial follicles than wild-type ovaries

• however, no significant change in seen at P2, indicating a normal size of primordial follicle pool at birth

decreased secondary ovarian follicle number ( J:75703 )

• at P7, ovaries contain significantly fewer preantral follicles than wild-type ovaries

• at P18, ovaries contain 40% fewer preantral and antral follicles than wild-type ovaries

• by P90, ovaries contain 3-fold fewer preantral and antral follicles than wild-type ovaries

decreased tertiary ovarian follicle number ( J:75703 )

• at P7, ovaries contain significantly fewer preantral and antral follicles than wild-type ovaries

• at P18, ovaries contain 40% fewer preantral and antral follicles than wild-type ovaries

• by P90, ovaries contain 3-fold fewer preantral and antral follicles than wild-type ovaries

impaired ovarian folliculogenesis ( J:75703 )

reduced female fertility ( J:75703 )

limbs/digits/tail

abnormal tarsal bone morphology ( J:68792 )

• about 30% of P1 mutants exhibit abnormal formation of tarsal bones

abnormal forelimb morphology ( J:68792 )

• although most of the bones in young mutants are normal, about 30% of P1 mice exhibit unilateral or bilateral angular distortion in their forelimbs due to abnormal formation of tarsal bones

integument

abnormal keratinocyte physiology ( J:59673 )

• primary keratinocytes in culture show reduced sensitivity to growth inhibition by TGF-beta and reduced adhesion to matrix and migration towards TGF-beta and keratinocyte growth factor

cellular

decreased B cell apoptosis ( J:140567 )

• bone marrow-derived, IL-7- dependent pro-B lymphocytes fail to exhibit a TGFbeta induced increased in apoptosis following a 24 or 48 hour treatment

hematopoietic system

abnormal leukocyte physiology ( J:59673 )

• monocytes show a selectively blunted chemotatic response to TGF-beta

decreased B cell apoptosis ( J:140567 )

• bone marrow-derived, IL-7- dependent pro-B lymphocytes fail to exhibit a TGFbeta induced increased in apoptosis following a 24 or 48 hour treatment

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteoarthritis		DOID:8398		J:68792

Allelic Composition	Smad3^tm1Cxd/Smad3^tm1Cxd
Genetic Background	involves: 129S6/SvEvTac * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad3^tm1Cxd mutation (0 available); any Smad3 mutation (18 available)

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

hematopoietic system

abnormal CD4-positive T cell differentiation ( J:136955 )

• nave CD4 T cells cultured under Th17-polarizing conditions produce about 3-fold less Th17 cells

• there is also less suppression of IL-21 producing T cells under Th17 polarizing conditions

immune system

abnormal CD4-positive T cell differentiation ( J:136955 )

• nave CD4 T cells cultured under Th17-polarizing conditions produce about 3-fold less Th17 cells

• there is also less suppression of IL-21 producing T cells under Th17 polarizing conditions

homeostasis/metabolism

increased circulating creatinine level ( J:137529 )

• homozygotes subjected to renal ischemia-reperfusion (IR) under sevoflurane anesthesia display significantly higher plasma creatinine levels than similarly treated wild-type mice

abnormal physiological response to xenobiotic ( J:137529 )

• sevoflurane fails to protect homozygotes against IR-induced renal tubular necrosis, unlike in wild-type controls

• sevoflurane also fails to protect primary cultures of renal proximal tubules against H2O2-induced necrosis, unlike in wild-type controls

increased susceptibility to kidney reperfusion injury ( J:137529 )

• homozygotes are not protected against renal IR injury under anesthesia with sevoflurane (a volatile anesthetic), unlike similarly treated wild-type controls

renal/urinary system

renal tubular necrosis ( J:137529 )

• homozygotes subjected to renal IR injury under sevoflurane anesthesia exhibit more severe renal tubular necrosis than similarly treated wild-type controls

• in culture, sevoflurane-treated proximal tubule cells isolated from homozygous mutant mice are not protected against H2O2-induced necrosis, unlike similarly treated wild-type proximal tubule cells

increased susceptibility to kidney reperfusion injury ( J:137529 )

• homozygotes are not protected against renal IR injury under anesthesia with sevoflurane (a volatile anesthetic), unlike similarly treated wild-type controls

cellular

renal tubular necrosis ( J:137529 )

• homozygotes subjected to renal IR injury under sevoflurane anesthesia exhibit more severe renal tubular necrosis than similarly treated wild-type controls

Allelic Composition	Smad2^tm1.1Epb/Smad2^tm1.1Epb Smad3^tm1Cxd/Smad3^tm1Cxd Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
Genetic Background	involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * DBA * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad2^tm1.1Epb mutation (1 available); any Smad2 mutation (50 available)
Smad3^tm1Cxd mutation (0 available); any Smad3 mutation (18 available)
Speer6-ps1^{Tg(Alb-cre)21Mgn} mutation (6 available); any Speer6-ps1 mutation (4 available)

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

liver/biliary system

liver/biliary system phenotype ( J:119642 )

N	• mice exhibit normal postnatal liver and body growth and function

cellular

abnormal cell morphology ( J:119642 )

• only a few hepatocytes attach with atypical morphology after seeding

abnormal cell physiology ( J:119642 )

• isolated primary hepatocytes show decreased viability immediately upon isolation, prior to plating (<70% viable cells) compared to controls or other mutant genotypes

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( J:119642 )

• injection of CCL4 to the liver induces a greater degree of liver injury in mice compared to control or individual single knockout mice; advanced bridging central injury is induced in livers

Allelic Composition	Smad2^tm1Cxd/Smad2⁺ Smad3^tm1Cxd/Smad3⁺
Genetic Background	involves: 129S6/SvEvTac * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad2^tm1Cxd mutation (0 available); any Smad2 mutation (50 available)
Smad3^tm1Cxd mutation (0 available); any Smad3 mutation (18 available)

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

craniofacial

abnormal Meckel's cartilage morphology ( J:76396 )

• E11 mandibular explants cultured in vitro form thinner Meckel's cartilage and show a developmental delay

skeleton

abnormal Meckel's cartilage morphology ( J:76396 )

• E11 mandibular explants cultured in vitro form thinner Meckel's cartilage and show a developmental delay

Allelic Composition	Smad2^tm1Cxd/Smad2⁺ Smad3^tm1Cxd/Smad3⁺
Genetic Background	involves: 129S6/SvEvTac * NIH Black Swiss

Find Mice

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:106308 )

• lethality by E14.5 due to hepatic dysplasia

embryonic lethality during organogenesis, incomplete penetrance ( J:70388 )

• 10 of 21 E8.5-E10.5 mutants suffer lethality due to patterning defects

growth/size/body

embryonic growth retardation ( J:106308 )

• severely affected mutants are growth retarded at E9.5

increased fetal size ( J:70388 )

• E14.5 mutants are somewhat larger in size

liver/biliary system

abnormal hepatoblast migration ( J:106308 )

• marker analysis indicates defects in hepatoblast migration

abnormal liver morphology ( J:70388 )

• liver architecture is distorted

• cultured livers from E10.5 mutants do not exhibit outgrowth of liver lobules with primitive bile ducts as in wild-type, instead, they suffer extensive cell death or fail to develop normal liver architecture

dilated liver sinusoidal space ( J:70388 )

• dilated sinusoidal spaces

delayed hepatic development ( J:106308 )

• marker analysis indicates a delay in hepatogenesis

abnormal hepatic cord morphology ( J:70388 )

• arrangement of hepatocytes is abnormal in E14.5 livers; hepatocytes are found in small clusters and cell plates are absent unlike in wild-type where cords of hepatocytes are distributed throughout in the parenchyma

small liver ( J:70388 )

• small livers but have the correct number of lobes and appear red

liver hypoplasia ( J:70388 , J:106308 )

• 100% of E14.5 mutants exhibit severe liver hypoplasia (J:70388)

• liver is reduced in some mutants at E12.5-E14.5 (J:106308)

abnormal hepatocyte physiology ( J:70388 )

• hepatocytes cultured in vitro fail to adhere well to various substrates, expression of beta1 integrin is lost, and E-cadherin is mislocalized, indicating that hepatocytes have abnormal adhesive properties

decreased hepatocyte proliferation ( J:70388 )

• liver cells are in a less proliferative state than in wild-type as indicated by PCNA antibody staining

hematopoietic system

increased erythrocyte cell number ( J:70388 )

• increase in the number of erythrocytes in E14.5 livers

craniofacial

abnormal craniofacial morphology ( J:70388 , J:106308 )

• 20% of E14.5 mutants exhibit craniofacial defects in addition to the liver hypoplaisa (J:70388)

• some embryos display craniofacial defects as early as E8.5 (J:106308)

cardiovascular system

dilated liver sinusoidal space ( J:70388 )

• dilated sinusoidal spaces

abnormal heart looping ( J:106308 )

• some embryos exhibit abnormal heart looping

abnormal pericardial cavity morphology ( J:106308 )

• some embryos exhibit an enlarged pericardiac cavity

digestive/alimentary system

abnormal foregut morphology ( J:106308 )

• anterior ventral foregut defects at E8.5 as indicated by marker analysis, showing that the definitive endoderm fails to displace the visceral endoderm at the anterior intestinal portal

embryo

abnormal developmental patterning ( J:106308 )

• 54 of 106 mutants display patterning abnormalities of varying severity at E9.5-E10.5

• some embryos display midline defects as early as E8.5

abnormal gastrulation ( J:106308 )

• gastrulation defects

abnormal endoderm development ( J:106308 )

• definitive endoderm is reduced at E8.5 as indicated by marker analysis

• mutants display defects in the specification of hepatogenic endoderm

embryonic growth retardation ( J:106308 )

• severely affected mutants are growth retarded at E9.5

abnormal somite development ( J:106308 )

• severely affected mutants exhibit irregular somites at E9.5

endocrine/exocrine glands

small thyroid gland ( J:106308 )

• reduced thyroid at E10.5

nervous system

holoprosencephaly ( J:106308 )

• seen in some mutants

vision/eye

cyclopia ( J:106308 )

• seen in some mutants

cellular

abnormal hepatoblast migration ( J:106308 )

• marker analysis indicates defects in hepatoblast migration

decreased hepatocyte proliferation ( J:70388 )

• liver cells are in a less proliferative state than in wild-type as indicated by PCNA antibody staining

Allelic Composition	Smad2^tm1.1Epb/Smad2^tm1.1Epb Smad3^tm1Cxd/Smad3^tm1Cxd
Genetic Background	involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * SJL

Find Mice

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

mortality/aging

premature death ( J:119642 )

• mice die between 1 and 8 months of age, due to primary defect in mucosal immune function

cellular

abnormal cell morphology ( J:119642 )

• after attachment to culture dishes, hepatocytes show relatively normal epithelial morphology but show wider cell-cell contacts and intracellular space compared to controls

decreased apoptosis ( J:119642 )

• after treatment with TGFbeta, cells show little or no apoptosis, compared to control or Smad2 conditional knockout cells

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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