All Phenotypes Smad5<tm1Zuk> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Smad5^tm1Zuk
targeted mutation 1, Martin M Matzuk
MGI:1857666

Summary

8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Smad5^tm1Zuk/Smad5^tm1Zuk	involves: 129S7/SvEvBrd * C57BL/6	MGI:2664826
ht2	Smad5^tm1Zuk/Smad5⁺	involves: 129S7/SvEvBrd * C57BL/6	MGI:2664827
cn3	Amhr2^tm3(cre)Bhr/Amhr2⁺ Smad1^tm2Rob/Smad1^tm2Rob Smad5^tm1Huy/Smad5^tm1Zuk	involves: 129P2/OlaHsd * 129S/SvEv * 129S7/SvEvBrd * C57BL/6	MGI:3769366
cn4	Amhr2^tm3(cre)Bhr/Amhr2⁺ Smad1^tm2Rob/Smad1^tm2Rob Smad5^tm1Huy/Smad5^tm1Zuk	involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6J	MGI:4437297
cn5	Amhr2^tm3(cre)Bhr/Amhr2⁺ Smad1^tm2Rob/Smad1^tm2Rob Smad5^tm1Huy/Smad5^tm1Zuk Smad9^tm1Jfm/Smad9^tm1Jfm	involves: 129S/SvEv * 129S4/SvJaeSor * C57BL/6	MGI:3769375
cx6	Smad1^tm1Rob/Smad1⁺ Smad5^tm1Zuk/Smad5⁺	involves: 129S/SvEv * 129S7/SvEvBrd	MGI:3702568
cx7	Smad5^tm1Zuk/Smad5⁺ Smad9^tm2.1Rob/Smad9^tm2.1Rob	involves: 129S/SvEv * 129S7/SvEvBrd	MGI:3702564
cx8	Smad1^tm1Rob/Smad1⁺ Smad5^tm1Zuk/Smad5⁺ Smad9^tm2.1Rob/Smad9^tm2.1Rob	involves: 129S/SvEv * 129S7/SvEvBrd	MGI:3702566

Allelic Composition	Smad5^tm1Zuk/Smad5^tm1Zuk
Genetic Background	involves: 129S7/SvEvBrd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad5^tm1Zuk mutation (1 available); any Smad5 mutation (23 available)

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:53293 )

• death between E9.5 and E11.5

cardiovascular system

abnormal blood vessel morphology ( J:53293 )

• dorsal aorta and vitelline vessels were dilated

• . ectopic vasculature and hematopoeisis occurs in the amnion

failure of heart looping ( J:60975 )

• mutant heart tubes failed to loop

abnormal heart tube morphology ( J:60975 )

• curvature of the heart tube was irregular and appeared to bend to accommodate longitudinal growth

delayed heart development ( J:53293 , J:60975 )

• severely delayed in most surviving embryos (J:53293)

digestive/alimentary system

abnormal digestive system development ( J:53293 )

• some embryos exhibited a vestigial foregut and hindgut

embryo

abnormal embryo development ( J:53293 )

• extreme anterior body curvature with a close head-to-tail apposition

abnormal embryo turning ( J:53293 , J:60975 )

• in the most severely affected embryos, turning never initiated and in older surviving embryos, turning was not complete or occurred in the opposite direction (J:53293)

• 53% of embryos failed to initiate turning and the remainder failed to complete turning (J:60975)

abnormal left-right axis patterning ( J:60975 )

• expression patterns of left-right axis determination genes was perturbed in addition to the heart looping and embryonic turning defects, suggesting that Smad5 is required for normal left-right axis determination

embryonic growth retardation ( J:53293 )

decreased embryo size ( J:53293 )

abnormal embryonic tissue morphology ( J:53293 )

• posterior region of embryo extended proximally far above the level of the head folds

• posterior regions were fragile and poorly developed in older surviving embryos

abnormal pharyngeal arch morphology ( J:53293 )

• underdeveloped appearance

delayed neural tube closure ( J:53293 )

• elayed cephalic neural tube closure; absent in some cases

• may be a secondary effect of heart defects since expression of neural markers was not altered between mutant embryos and controls

abnormal allantois morphology ( J:53293 )

• poorly elongated allantois with an enlarged base

abnormal amnion morphology ( J:53293 )

• at E8.0-E8.5, some embryos showed abnormal amnion morphology; others exhibited cell aggregates at later stages that appeared to be derived from extraembryonic mesoderm

• at E9.5, hemorrhagic structures were observed

• ectopic vasculature and hematopoeisis occurs in the amnion

pale yolk sac ( J:53293 )

• yolk sac had anemic appearance

abnormal vitelline vascular remodeling ( J:53293 )

• yolk sacs lacked networks of branching vitelline vessels, but did contain a primitive plexus

growth/size/body

embryonic growth retardation ( J:53293 )

decreased embryo size ( J:53293 )

abnormal ventral body wall morphology ( J:53293 )

• heart not enclosed by the body wall, remaining exteriorized

• in older embryos, the posterior body wall remains open (the lateral body wall rarely closed around the ventral midgut region)

homeostasis/metabolism

edema ( J:53293 )

• generalized, likely due to vascular defects

reproductive system

decreased primordial germ cell number ( J:70069 )

• reduced number of primordial germ cells (PGCs)

• on average, 8 PGCs were detected in embyros with 0 to 5 somites (age matched wild-type mice had 65 PGCs)

• PGCs were undetected in ~20% of mice

• ectopic PGCs were observed in the amnion of some mice

nervous system

delayed neural tube closure ( J:53293 )

• elayed cephalic neural tube closure; absent in some cases

• may be a secondary effect of heart defects since expression of neural markers was not altered between mutant embryos and controls

abnormal brain development ( J:53293 )

• in severely affected embryos, development of the prosencephalon and the optic sulcus was delayed

exencephaly ( J:53293 )

• in severely affected embryos, due to failure of neural tube closure

craniofacial

abnormal pharyngeal arch morphology ( J:53293 )

• underdeveloped appearance

cellular

decreased primordial germ cell number ( J:70069 )

• reduced number of primordial germ cells (PGCs)

• on average, 8 PGCs were detected in embyros with 0 to 5 somites (age matched wild-type mice had 65 PGCs)

• PGCs were undetected in ~20% of mice

• ectopic PGCs were observed in the amnion of some mice

Allelic Composition	Smad5^tm1Zuk/Smad5⁺
Genetic Background	involves: 129S7/SvEvBrd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad5^tm1Zuk mutation (1 available); any Smad5 mutation (23 available)

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

reproductive system

decreased primordial germ cell number ( J:70069 )

• on average, 45 PGCs were detected in embyros with 0 to 5 somites (age matched wild-type mice had 65 PGCs)

reduced fertility ( J:70069 )

decreased litter size ( J:70069 )

cellular

decreased primordial germ cell number ( J:70069 )

• on average, 45 PGCs were detected in embyros with 0 to 5 somites (age matched wild-type mice had 65 PGCs)

Allelic Composition	Amhr2^tm3(cre)Bhr/Amhr2⁺ Smad1^tm2Rob/Smad1^tm2Rob Smad5^tm1Huy/Smad5^tm1Zuk
Genetic Background	involves: 129P2/OlaHsd * 129S/SvEv * 129S7/SvEvBrd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Amhr2^tm3(cre)Bhr mutation (1 available); any Amhr2 mutation (29 available)
Smad1^tm2Rob mutation (1 available); any Smad1 mutation (32 available)
Smad5^tm1Huy mutation (0 available); any Smad5 mutation (23 available)
Smad5^tm1Zuk mutation (1 available); any Smad5 mutation (23 available)

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

mortality/aging

early reproductive senescence ( J:128934 )

• female mice become infertile after 3 to 4 months of breeding

reproductive system

increased ovary tumor incidence ( J:128934 )

• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors

increased ovarian carcinoma incidence ( J:128934 )

• over 70% of female mice have metastic ovarian cancer by 1 year of age

increased testis tumor incidence ( J:128934 )

• 100% of male mice by 7 months of age exhibit tumors in the testis

• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation

early reproductive senescence ( J:128934 )

• female mice become infertile after 3 to 4 months of breeding

male infertility ( J:128934 )

• slight infertility, with a 16% decrease in litters per month when bred to wild-type females

neoplasm

increased ovary tumor incidence ( J:128934 )

• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors

increased ovarian carcinoma incidence ( J:128934 )

• over 70% of female mice have metastic ovarian cancer by 1 year of age

increased testis tumor incidence ( J:128934 )

• 100% of male mice by 7 months of age exhibit tumors in the testis

• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation

cardiovascular system

hemoperitoneum ( J:128934 )

• found in 50% of female mice over 9 months in age

• found in about 60% of male mice by 11 months in age

endocrine/exocrine glands

increased ovary tumor incidence ( J:128934 )

• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors

increased ovarian carcinoma incidence ( J:128934 )

• over 70% of female mice have metastic ovarian cancer by 1 year of age

increased testis tumor incidence ( J:128934 )

• 100% of male mice by 7 months of age exhibit tumors in the testis

• early stage tumors appear to be sex cord stromal tumors with Sertoli and Leydig cell differentiation

Allelic Composition	Amhr2^tm3(cre)Bhr/Amhr2⁺ Smad1^tm2Rob/Smad1^tm2Rob Smad5^tm1Huy/Smad5^tm1Zuk
Genetic Background	involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6J

Find Mice

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

mortality/aging

premature death ( J:157310 )

• 33% of mutant females survived to 32 weeks

• 50% survival at approximately 29 week of age

neoplasm

increased granulosa cell tumor incidence ( J:157310 )

• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)

• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level

• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary

homeostasis/metabolism

suppressed circulating follicle stimulating hormone level ( J:157310 )

endocrine/exocrine glands

increased granulosa cell tumor incidence ( J:157310 )

• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)

• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level

• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary

reproductive system

increased granulosa cell tumor incidence ( J:157310 )

• develop granulosa cell tumors early during sexual maturity (at least by 8 wk of age)

• tumor characteristic: lacked nuclear grooves, infrequently contained Call-Exner bodies, high mitotic index, increased serum Inhibin A and anti-Mullerian hormone (AMH) level

• AMH expression in primary tumors and tumor cells as they metastasize outside the ovary

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ovarian cancer		DOID:2394	OMIM:167000 OMIM:607893	J:157310

Allelic Composition	Amhr2^tm3(cre)Bhr/Amhr2⁺ Smad1^tm2Rob/Smad1^tm2Rob Smad5^tm1Huy/Smad5^tm1Zuk Smad9^tm1Jfm/Smad9^tm1Jfm
Genetic Background	involves: 129S/SvEv * 129S4/SvJaeSor * C57BL/6

Find Mice

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

endocrine/exocrine glands

increased ovary tumor incidence ( J:128934 )

• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors

increased ovarian carcinoma incidence ( J:128934 )

• over 70% of female mice have metastic ovarian cancer by 1 year of age

mortality/aging

early reproductive senescence ( J:128934 )

• female mice become infertile after 3 to 4 months of breeding

reproductive system

increased ovary tumor incidence ( J:128934 )

• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors

increased ovarian carcinoma incidence ( J:128934 )

• over 70% of female mice have metastic ovarian cancer by 1 year of age

early reproductive senescence ( J:128934 )

• female mice become infertile after 3 to 4 months of breeding

neoplasm

increased ovary tumor incidence ( J:128934 )

• after 3 months of age, 100% of female mice have unilateral or bilateral ovarian tumors

increased ovarian carcinoma incidence ( J:128934 )

• over 70% of female mice have metastic ovarian cancer by 1 year of age

cardiovascular system

hemoperitoneum ( J:128934 )

• found in 50% of female mice over 9 months in age

Allelic Composition	Smad1^tm1Rob/Smad1⁺ Smad5^tm1Zuk/Smad5⁺
Genetic Background	involves: 129S/SvEv * 129S7/SvEvBrd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad1^tm1Rob mutation (0 available); any Smad1 mutation (32 available)
Smad5^tm1Zuk mutation (1 available); any Smad5 mutation (23 available)

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:119296 )

• no viable embryos are recovered at E13.5

embryo

absent second pharyngeal arch ( J:119296 )

• second branchial arches are absent or severely compromised in their development

absent third pharyngeal arch ( J:119296 )

• third branchial arches are absent or severely compromised in their development

abnormal mesoderm development ( J:119296 )

• in the most severely affected mutants, mesoderm is underrepresented

abnormal left-right axis patterning ( J:119296 )

• expression of Nodal in embryos is disturbed in lateral plate mesoderm (LPM), showing compromised ability to activate left/right pathway in LPM

abnormal rostral-caudal axis patterning ( J:119296 )

• at E10.5 and 11.5, the most severely affected embryos (~33%) are poorly patterned along the anterior-posterior axis

incomplete rostral neuropore closure ( J:119296 )

• in some embryos, rostral regions of CNS tissue are correctly specified, but cranial folds fail to fuse

abnormal somite development ( J:119296 )

• somites are misaligned and fragmented in a high proportion of embryos

abnormal allantois morphology ( J:119296 )

• in many embryos, morphology is overtly normal except that allantois remains as a dense mass of tissue

• in some embryos the allantois is fused across the amnion

excessive folding of visceral yolk sac ( J:119296 )

• some embryos at E7.5 display ruffling of the visceral yolk sac

cardiovascular system

abnormal heart development ( J:119296 )

• heart chamber patterning and specification is severely disturbed

abnormal heart looping ( J:119296 )

• pronounced heart looping defects are observed in a high proportion of embryos

abnormal direction of heart looping ( J:119296 )

• in some embryos, there is inversion of looping direction

failure of heart looping ( J:119296 )

• in some embryos, looping is stalled, with heart tube remaining linear along ventral midline

abnormal heart tube morphology ( J:119296 )

• anterior-posterior patterning of heart tube is abnormal

nervous system

abnormal forebrain morphology ( J:119296 )

• in the most severely affected embryos, there is a spectrum of anterior defects; embryos show absence of anterior-most neural tissue by Fgf8 expression, whereas midbrain-hindbrain isthmus is specified

abnormal nervous system development ( J:119296 )

• most rostral regions of CNS are absent

incomplete rostral neuropore closure ( J:119296 )

• in some embryos, rostral regions of CNS tissue are correctly specified, but cranial folds fail to fuse

reproductive system

decreased primordial germ cell number ( J:119296 )

• at the 10-15 somite stage, mutants show greatly reduced numbers of primordial germ cells (PGCs) compared to wild-type (wild-type 80-100 cells)

• at 20-25 somite stage, there are 200-300 germ cells in hindgut in wild-type, most mutants lack germ cells and remainder (~40%) show 10-fold fewer cells

absent primordial germ cells ( J:119296 )

• in majority of embryos at the 20-25 somite stage, germ cells are absent

craniofacial

absent second pharyngeal arch ( J:119296 )

• second branchial arches are absent or severely compromised in their development

absent third pharyngeal arch ( J:119296 )

• third branchial arches are absent or severely compromised in their development

cellular

decreased primordial germ cell number ( J:119296 )

• at the 10-15 somite stage, mutants show greatly reduced numbers of primordial germ cells (PGCs) compared to wild-type (wild-type 80-100 cells)

• at 20-25 somite stage, there are 200-300 germ cells in hindgut in wild-type, most mutants lack germ cells and remainder (~40%) show 10-fold fewer cells

absent primordial germ cells ( J:119296 )

• in majority of embryos at the 20-25 somite stage, germ cells are absent

Allelic Composition	Smad5^tm1Zuk/Smad5⁺ Smad9^tm2.1Rob/Smad9^tm2.1Rob
Genetic Background	involves: 129S/SvEv * 129S7/SvEvBrd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad5^tm1Zuk mutation (1 available); any Smad5 mutation (23 available)
Smad9^tm2.1Rob mutation (0 available); any Smad9 mutation (32 available)

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:119296 )

• authors state phenotype is same as previously described for Smad5 null embryos; Smad9 deficiency does not exacerbate the Smad5 phenotype

embryo

abnormal embryo development ( J:119296 )

abnormal extraembryonic tissue morphology ( J:119296 )

growth/size/body

abnormal embryonic growth/weight/body size ( J:119296 )

cardiovascular system

abnormal blood vessel morphology ( J:119296 )

abnormal heart development ( J:119296 )

nervous system

abnormal nervous system development ( J:119296 )

craniofacial

abnormal craniofacial development ( J:119296 )

reproductive system

abnormal germ cell morphology ( J:119296 )

cellular

abnormal germ cell morphology ( J:119296 )

Allelic Composition	Smad1^tm1Rob/Smad1⁺ Smad5^tm1Zuk/Smad5⁺ Smad9^tm2.1Rob/Smad9^tm2.1Rob
Genetic Background	involves: 129S/SvEv * 129S7/SvEvBrd

Find Mice

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

mortality/aging

prenatal lethality, complete penetrance ( J:119296 )

• no live born mice are obtained

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