Phenotypes associated with this allele

• Allele Symbol: Smad4^tm1.1Rob
• Allele Name: targeted mutation 1.1, Elizabeth J Robertson
• Allele ID: MGI:3624263
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Smad4^tm1.1Rob/Smad4^tm1.1Rob	involves: 129S/SvEv * CD-1	MGI:3624714
ht2	Smad4^tm1.1Rob/Smad4^+	involves: 129S/SvEv * CD-1	MGI:3624715
ht3	Smad4^tm1.1Rob/Smad4^tm2.1Rob	involves: 129S/SvEv * C57BL/6	MGI:3819927
cn4	Smad4^tm1Rob/Smad4^tm1.1Rob Tg(Hoxb7-cre)1Rob/0	involves: 129S/SvEv	MGI:3628945
cn5	Amhr2^tm3(cre)Bhr/Amhr2^+ Smad4^tm1Rob/Smad4^tm1.1Rob	involves: 129S/SvEv * C57BL/6J	MGI:3624725
cn6	Bmp7^tm6(cre)Rob/Bmp7^+ Smad4^tm1Rob/Smad4^tm1.1Rob	involves: 129S/SvEv * C57BL/6 * SJL	MGI:3628946
cn7	Smad4^tm1Rob/Smad4^tm1.1Rob Edil3^Tg(Sox2-cre)1Amc/Edil3^+	involves: 129S/SvEv * CD-1	MGI:3624716

Genotype
MGI:3624714

hm1

• Allelic Composition: Smad4^tm1.1Rob/Smad4^tm1.1Rob
• Genetic Background: involves: 129S/SvEv * CD-1

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

embryo

abnormal endoderm development ( J:92066 )

• at E6.5 mutants have a thickened endoderm

abnormal proximal-distal axis patterning ( J:92066 )

• at E6.5, homozygotes have a shortened proximal-distal axis

abnormal embryonic epiblast morphology ( J:92066 )

• disorganization of epiblast is observed at E6.5

abnormal visceral endoderm morphology ( J:92066 )

• disorganization of epiblast and overlying visceral endoderm is observed at E6.5

Genotype
MGI:3624715

ht2

• Allelic Composition: Smad4^tm1.1Rob/Smad4⁺
• Genetic Background: involves: 129S/SvEv * CD-1

neoplasm

increased stomach tumor incidence ( J:92066 )

• aged heterozygotes develop gastric tumors

digestive/alimentary system

increased stomach tumor incidence ( J:92066 )

• aged heterozygotes develop gastric tumors

Genotype
MGI:3819927

ht3

• Allelic Composition: Smad4^tm1.1Rob/Smad4^tm2.1Rob
• Genetic Background: involves: 129S/SvEv * C57BL/6

normal phenotype

no abnormal phenotype detected ( J:141589 )

Genotype
MGI:3628945

cn4

• Allelic Composition: Smad4^tm1Rob/Smad4^tm1.1Rob; Tg(Hoxb7-cre)1Rob/0
• Genetic Background: involves: 129S/SvEv

mortality/aging

premature death ( J:108109 )

• by 8 weeks of age 3 of 8 mice had died

renal/urinary system

renal/urinary system phenotype ( J:108109 )

N • at E16.5 kidneys appear morphologically similar to control mice

Genotype
MGI:3624725

cn5

• Allelic Composition: Amhr2^tm3(cre)Bhr/Amhr2⁺; Smad4^tm1Rob/Smad4^tm1.1Rob
• Genetic Background: involves: 129S/SvEv * C57BL/6J

cellular

decreased oocyte number ( J:108954 )

♀ • superovulated mutant females show a significant reduction in numbers of oocytes collected from the oviducts compared to controls

homeostasis/metabolism

increased circulating progesterone level ( J:108954 )

reproductive system

decreased oocyte number ( J:108954 )

♀ • superovulated mutant females show a significant reduction in numbers of oocytes collected from the oviducts compared to controls

abnormal ovarian follicle morphology ( J:108954 )

♀ • ovaries of knockout animals often contain small follicles with luteinizing cells surrounding either oocytes or oocyte remnants

abnormal granulosa cell morphology ( J:108954 )

♀ • some secondary stage follicles show oocytes without associated granulosa cells

decreased tertiary ovarian follicle number ( J:108954 )

♀ • in knockout mice, there are fewer large antral follicles

abnormal ovarian folliculogenesis ( J:108954 )

♀ • in knockout females, large follicle-like structures enclosing a trapped oocyte are observed

♀ • in superovulated females, some follicles show oocytes lacking cumulus cells

abnormal cumulus expansion ( J:108954 )

♀ • in superovualated females, half as many intact cumulus-oocyte complexes are recovered from large antral follicles after 44 hours compared to controls

♀ • cumulus-oocyte complexes isolated from mutant females show reduced or absent cumulus expansion when cultured in the presence of serum and FSH

absent cumulus expansion ( J:108954 )

♀ • cumulus-oocyte complexes isolated from mutant females may show absent cumulus expansion when cultured in the presence of serum and FSH

abnormal secondary ovarian follicle morphology ( J:108954 )

♀ • some secondary stage follicles show oocytes without associated granulosa cells

increased secondary ovarian follicle number ( J:108954 )

♀ • in knockout mice, there are more preantral follicles

decreased ovulation rate ( J:108954 )

♀ • mutant females ovulate about half as much as wild-type

decreased litter size ( J:108954 )

• null mice have an average of 1.3 pups per litter over a 6-month period, compared to 10.4 pups/litter for control Smad4^tm1.1Rob/Smad4^tm1Rob animals which is not different from wild-type litter size

infertility ( J:108954 )

• at 3 months of age, 25% of breeding females are infertile; by 6 months of age, 50% are infertile

endocrine/exocrine glands

abnormal ovarian follicle morphology ( J:108954 )

♀ • ovaries of knockout animals often contain small follicles with luteinizing cells surrounding either oocytes or oocyte remnants

abnormal granulosa cell morphology ( J:108954 )

♀ • some secondary stage follicles show oocytes without associated granulosa cells

decreased tertiary ovarian follicle number ( J:108954 )

♀ • in knockout mice, there are fewer large antral follicles

abnormal ovarian folliculogenesis ( J:108954 )

♀ • in knockout females, large follicle-like structures enclosing a trapped oocyte are observed

♀ • in superovulated females, some follicles show oocytes lacking cumulus cells

abnormal cumulus expansion ( J:108954 )

♀ • in superovualated females, half as many intact cumulus-oocyte complexes are recovered from large antral follicles after 44 hours compared to controls

♀ • cumulus-oocyte complexes isolated from mutant females show reduced or absent cumulus expansion when cultured in the presence of serum and FSH

absent cumulus expansion ( J:108954 )

♀ • cumulus-oocyte complexes isolated from mutant females may show absent cumulus expansion when cultured in the presence of serum and FSH

abnormal secondary ovarian follicle morphology ( J:108954 )

♀ • some secondary stage follicles show oocytes without associated granulosa cells

increased secondary ovarian follicle number ( J:108954 )

♀ • in knockout mice, there are more preantral follicles

Genotype
MGI:3628946

cn6

• Allelic Composition: Bmp7^tm6(cre)Rob/Bmp7⁺; Smad4^tm1Rob/Smad4^tm1.1Rob
• Genetic Background: involves: 129S/SvEv * C57BL/6 * SJL

mortality/aging

perinatal lethality, incomplete penetrance ( J:108109 )

• only 7% of pups at P1 are homozygous rather than the expected 25%

postnatal lethality, complete penetrance ( J:108109 )

• at 1 week of age no pups are found

renal/urinary system

kidney cyst ( J:108109 )

• sporadic cysts at E17.5 sometimes occurring in Bowman's space

decreased kidney collecting duct number ( J:108109 )

• the number of collecting ducts is reduced to 8 +/- 1 and 9 +/- 2 compared to 20 +/- 2 and 28 +/- 2 in wild-type mice at E14.5 and E16.5, respectively

abnormal renal glomerulus morphology ( J:108109 )

• abnormal clustering of the glomeruli

abnormal kidney development ( J:108109 )

• at E12.0, E14.5, and E16.5 increased cell death is seen in thickened areas of the mesenchyme at the periphery of the kidney; however around the collecting duct tips cell death is similar to wild-type

• at E12.5 expression patterns indicate that few foci of nephrogenic mesenchyme condensations are formed, the stromal cell population is increased, the number of epithelial structures is reduced, and the normal segregation of stoma and mesenchyme is incomplete

• at E12.5 the cortical cell layer is thicker than in wild-type and increased cell death is seen in the cortical regions

• at E14.5 the cell layer between the nephrogenic mesenchyme and the kidney capsule is thicker than in wild-type

• at E14.5 and E16.5 the tips of the collecting ducts are surrounded by variably reduced amounts of nephrogenic mesenchyme with about 50% lacking any surrounding nephrogenic mesenchyme

small kidney ( J:108109 )

• about half the volume of wild-type kidneys at E17.5

hydroureter ( J:108109 )

• at E17.5

growth/size/body

kidney cyst ( J:108109 )

• sporadic cysts at E17.5 sometimes occurring in Bowman's space

Genotype
MGI:3624716

cn7

• Allelic Composition: Smad4^tm1Rob/Smad4^tm1.1Rob; Edil3^{Tg(Sox2-cre)1Amc}/Edil3⁺
• Genetic Background: involves: 129S/SvEv * CD-1

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:92066 )

• at E9.5, mutant embryos show significant degeneration; no mutants are recovered at E10

embryo

abnormal dorsal-ventral axis patterning ( J:92066 )

• at E8.5, mutants shave a flattened ventral surface with no visible fore- or hindgut formation and caudally displaced bulbous neural tissue

abnormal rostral-caudal axis patterning ( J:92066 )

• after E7, the anterior-posterior axis is broadened

• at E7.5 and early head fold stages, embryo adopts and elongated and distorted 'boot-shaped' morphology; mutants show rudimentary anterior neural development with no visible headfolds and recognizable foregut invagination

abnormal rhombomere morphology ( J:92066 )

• mutant embryos exhibit abnormal rhombomere morphology

fused somites ( J:92066 )

• somites form, but are fused across the midline

abnormal allantois morphology ( J:92066 )

• all mutants show an allantois-like outgrowth of variable size and in 70% of the cases associates with the stalk-like chorionic ectoderm while in the remaining embryos, the allantois terminates blindly in the exocoelomic cavity

nervous system

abnormal hindbrain development ( J:92066 )

• mutant embryos exhibit abnormal hindbrain development

abnormal rhombomere morphology ( J:92066 )

• mutant embryos exhibit abnormal rhombomere morphology

reproductive system

absent primordial germ cells ( J:92066 )

• most embryos lack primordial germ cells which form at the base of the primordial allantois

digestive/alimentary system

absent foregut ( J:92066 )

• no visible formation of foregut at E8.5

absent hindgut ( J:92066 )

• no visible formation of hindgut at E8.5

cellular

absent primordial germ cells ( J:92066 )

• most embryos lack primordial germ cells which form at the base of the primordial allantois