Phenotypes associated with this allele

• Allele Symbol: Wnt3a^tm1Amc
• Allele Name: targeted mutation 1, Andrew P McMahon
• Allele ID: MGI:1857489
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Wnt3a^tm1Amc/Wnt3a^tm1Amc	involves: 129S1/Sv	MGI:2169171
hm2	Wnt3a^tm1Amc/Wnt3a^tm1Amc	involves: 129S1/Sv * C57BL/6J	MGI:3587997
ht3	Wnt3a^tm1Amc/Wnt3a^vt	involves: 129S1/Sv * C3H/HeJ * C57BL/6J * C57BR	MGI:3604385
cx4	Tbx6^tm2Pa/Tbx6^+ Wnt3a^tm1Amc/Wnt3a^+	involves: 129 * 129S1/Sv * 129X1/SvJ * ICR	MGI:3804667
cx5	Fzd2^tm1.1Nat/Fzd2^+ Fzd7^tm1.1Nat/Fzd7^tm1.1Nat Wnt3a^tm1Amc/Wnt3a^+	involves: 129 * C57BL/6	MGI:5444714
cx6	Fzd7^tm1.1Nat/Fzd7^tm1.1Nat Wnt3a^tm1Amc/Wnt3a^+	involves: 129 * C57BL/6	MGI:5444713
cx7	Wnt1^tm1Brd/Wnt1^tm1Brd Wnt3a^tm1Amc/Wnt3a^tm1Amc	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:2166755

Genotype
MGI:2169171

hm1

• Allelic Composition: Wnt3a^tm1Amc/Wnt3a^tm1Amc
• Genetic Background: involves: 129S1/Sv

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

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:69781 )

• most homozygotes die around E10.5, but a few survive until just before birth

skeleton

kyphosis ( J:69781 )

• seen in surviving embryos at E18.5

abnormal cervical vertebrae morphology ( J:69781 )

abnormal cervical axis morphology ( J:69781 )

• cervical vertebra 2 (C2) is fused to C1 in the dorsal region

• C2 has the anterior arcus atlantis that is normally seen on the ventral part of C1

cervical vertebral transformation ( J:69781 )

• homeotic transformation of cervical vertebra 2 (C2) to C1

• C2 has the anterior arcus atlantis that is normally seen on the ventral part of C1

embryo

sirenomelia ( J:69781 )

• truncation caudal to the forelimb level

abnormal somite development ( J:31335 )

• only abnormal somite formation is seen posterior to the forelimb bud

limbs/digits/tail

sirenomelia ( J:69781 )

• truncation caudal to the forelimb level

Genotype
MGI:3587997

hm2

• Allelic Composition: Wnt3a^tm1Amc/Wnt3a^tm1Amc
• Genetic Background: involves: 129S1/Sv * C57BL/6J

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:16716 )

• homozygous mutant embryos die between E10.5 and E12.5

embryo

abnormal gastrulation ( J:16716 )

• at E9.5, severe axial truncations suggest impaired gastrulation

abnormal mesoderm development ( J:16716 )

• homozygous mutant embryos exhibit impaired dorsal mesoderm development

abnormal rostral-caudal axis patterning ( J:16716 )

• at E9.5, mutants show massive cell death in the caudal-most region of the axis; cell death is mainly restricted to the dorsal-most mesodermal cells

• at E12.5, caudal development terminates at the level of umbilicus, just anterior to where hindlimbs normally form

caudal body truncation ( J:16716 )

• at E9.5, all mutant embryos exhibit severe axial truncation; however, yolk sac mesoderm and allantois formation appears unaffected

• by E12.5, mutants with little or no caudal development posterior to the forelimb display massive axial truncation

kinked neural tube ( J:16716 )

• at E9.5, mutant embryos have a severely kinked and folded neural tube

• at E9.75, dorsal fusion of the neural tube is often absent

truncated notochord ( J:16716 )

• at E9.5, mutant notochord is present at the level of forelimbs, but is missing or disrupted in more posterior regions just caudal to the forelimb buds

incomplete somite formation ( J:16716 )

• at E9.5, formation of the first 7 to 9 somites up to the level of the forelimb bud is normal; however, no somites are detected from the forelimbs caudal

absent tail bud ( J:16716 )

• at E9.5, homozygous mutant embryos lack a visible tail bud formation

nervous system

abnormal nervous system morphology ( J:16716 )

• mutant embryos exhibit abnormal CNS morphology and ectopic expression of a dorsal CNS maker

kinked neural tube ( J:16716 )

• at E9.5, mutant embryos have a severely kinked and folded neural tube

• at E9.75, dorsal fusion of the neural tube is often absent

abnormal spinal cord morphology ( J:16716 )

• at E9.5, the mutant spinal cord is severely dysmorphic (kinked)

growth/size/body

decreased body length ( J:16716 )

• at E9.5, mutant embryos display a shortened trunk caudal to the forelimbs; anterior development proceeds normally

limbs/digits/tail

absent tail bud ( J:16716 )

• at E9.5, homozygous mutant embryos lack a visible tail bud formation

absent tail ( J:16716 )

• at E12.5, mutants occasionally display a small degenerate structure just caudal to the forelimbs, i.e. a single midline hindlimb in the normal position of the tail

Genotype
MGI:3604385

ht3

• Allelic Composition: Wnt3a^tm1Amc/Wnt3a^vt
• Genetic Background: involves: 129S1/Sv * C3H/HeJ * C57BL/6J * C57BR

mortality/aging

premature death ( J:31335 )

• only about 50% of compound heterozygotes live longer than 4 weeks compared to 90% of Wnt3a^vt heterozygotes

limbs/digits/tail

absent tail ( J:31335 )

skeleton

abnormal thoracic vertebrae morphology ( J:31335 )

• deformities seen as far anterior as the 7th thoracic vertebra

decreased thoracic vertebrae number ( J:31335 )

• the most severely affected mutants have a reduction in the number of thoracic vertebrae

decreased lumbar vertebrae number ( J:31335 )

• none of the compound heterozygotes have all of the lumbar vertebrae

absent sacral vertebrae ( J:31335 )

• no normal sacral vertebrae are seen

embryo

decreased embryo size ( J:31335 )

• the most severely affected mutants are smaller than wild-type littermates

spina bifida ( J:31335 )

• the most severely affected mutants display spina bifida of the posterior neural tube

abnormal somite development ( J:31335 )

• somites do not extend as far caudally as in wild-type embryos and malformed somites are seen rostral to the last somite

nervous system

spina bifida ( J:31335 )

• the most severely affected mutants display spina bifida of the posterior neural tube

behavior/neurological

hindlimb paralysis ( J:31335 )

• the most severely affected mutants display hindlimb paralysis

growth/size/body

decreased embryo size ( J:31335 )

• the most severely affected mutants are smaller than wild-type littermates

renal/urinary system

abnormal urination ( J:31335 )

• in several cases severely affected mutants displayed accumulation of urine in the kidneys and ureters

digestive/alimentary system

abnormal intestine morphology ( J:31335 )

• in several cases severely affected mutants displayed hyperextended intestines

Genotype
MGI:3804667

cx4

• Allelic Composition: Tbx6^tm2Pa/Tbx6⁺; Wnt3a^tm1Amc/Wnt3a⁺
• Genetic Background: involves: 129 * 129S1/Sv * 129X1/SvJ * ICR

embryo

embryo phenotype ( J:137163 )

N • despite decrease in Wnt3a expression in Tbx6 null mice, no defects in somite formation are detected

cardiovascular system

cardiovascular system phenotype ( J:137163 )

N • unlike in Tbx6 null mice, the direction of heart looping is similar to controls

Genotype
MGI:5444714

cx5

• Allelic Composition: Fzd2^tm1.1Nat/Fzd2⁺; Fzd7^tm1.1Nat/Fzd7^tm1.1Nat; Wnt3a^tm1Amc/Wnt3a⁺
• Genetic Background: involves: 129 * C57BL/6

cardiovascular system

abnormal heart morphology ( J:189062 )

• 92% of embryos (n=12) display cardiac defects

ventricular septal defect ( J:189062 )

• most defects are VSDs

craniofacial

cleft palate ( J:189062 )

• in 14% of embryos (n=14)

digestive/alimentary system

cleft palate ( J:189062 )

• in 14% of embryos (n=14)

growth/size/body

cleft palate ( J:189062 )

• in 14% of embryos (n=14)

Genotype
MGI:5444713

cx6

• Allelic Composition: Fzd7^tm1.1Nat/Fzd7^tm1.1Nat; Wnt3a^tm1Amc/Wnt3a⁺
• Genetic Background: involves: 129 * C57BL/6

cardiovascular system

abnormal heart morphology ( J:189062 )

• 37% of embryos (n=16) display cardiac defects

ventricular septal defect ( J:189062 )

• most defects are VSDs

Genotype
MGI:2166755

cx7

• Allelic Composition: Wnt1^tm1Brd/Wnt1^tm1Brd; Wnt3a^tm1Amc/Wnt3a^tm1Amc
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:44094 )

• double homozygotes are obtained at the expected Mendelian frequency between E9.0 and E10.5; however, only a few survive to E18.5

embryonic lethality during organogenesis, incomplete penetrance ( J:44094 )

• double homozygotes are obtained at the expected Mendelian frequency between E9.0 and E10.5; however, only a few survive to E18.5

nervous system

abnormal neural crest cell morphology ( J:44094 )

• double homozygotes show defects in major neural crest derivatives, including components of the head skeleton, cranial and dorsal root ganglia, and melanocyte precursors, suggesting that a broad loss of dorsal Wnt signaling in the neural tube affects neural crest formation

abnormal melanoblast morphology ( J:44094 )

• at E11.5, double homozygotes show show virtual loss of dopachrome tautomerase-positive (DCT+), neural crest-derived melanoblasts within the hindbrain region; a few DCT+ cells remain at the dorsal midline

abnormal forebrain development ( J:44094 )

• at E9.0, double homozygotes exhibit loss of forebrain tissue

abnormal midbrain development ( J:44094 )

• at E9.0, double homozygotes exhibit loss of midbrain tissue

abnormal metencephalon morphology ( J:44094 )

• at E9.0. double homozygotes exhibit loss of rostral hindbrain r1, which is typical of Wnt3a^tm1Amc homozygotes

small dorsal root ganglion ( J:44094 )

• at E10.5, double homozygotes show a 60% reduction in the cellular content of the dorsal root ganglia; in contrast, sympathetic ganglia remain normal

skeleton

small basisphenoid bone ( J:44094 )

• at E18.5, the basisphenoid bone is somewhat reduced

small alisphenoid bone ( J:44094 )

• at E18.5, the alisphenoid bone is somewhat reduced

small presphenoid bone ( J:44094 )

• at E18.5, the presphenoid bone is somewhat reduced

small temporal bone squamous part ( J:44094 )

• at E18.5, the squamosal bone is somewhat reduced

absent hyoid bone ( J:44094 )

• at E18.5, the main body of the hyoid bone including the greater horn, which originates from neural crest cells derived from r6-r7, is absent

absent stapes ( J:44094 )

• at E18.5, the stapes, which originates from neural crest cells derived from r3-r5, is absent

abnormal thyroid cartilage morphology ( J:44094 )

• at E18.5, the thyroid cartilage is consistently malformed

embryo

abnormal dorsal-ventral axis patterning ( J:44094 )

• double homozygotes display a severe reduction of dorsolateral neural precursors within the neural tube

caudal body truncation ( J:44094 )

• similar to Wnt3a^tm1Amc homozygotes, double homozygotes exhibit severe posterior axial truncation at the forelimb level

abnormal neural crest cell morphology ( J:44094 )

• double homozygotes show defects in major neural crest derivatives, including components of the head skeleton, cranial and dorsal root ganglia, and melanocyte precursors, suggesting that a broad loss of dorsal Wnt signaling in the neural tube affects neural crest formation

abnormal melanoblast morphology ( J:44094 )

• at E11.5, double homozygotes show show virtual loss of dopachrome tautomerase-positive (DCT+), neural crest-derived melanoblasts within the hindbrain region; a few DCT+ cells remain at the dorsal midline

hearing/vestibular/ear

absent stapes ( J:44094 )

• at E18.5, the stapes, which originates from neural crest cells derived from r3-r5, is absent

small otic capsule ( J:44094 )

• at E18.5, the otic capsule is somewhat reduced

craniofacial

small basisphenoid bone ( J:44094 )

• at E18.5, the basisphenoid bone is somewhat reduced

small alisphenoid bone ( J:44094 )

• at E18.5, the alisphenoid bone is somewhat reduced

small presphenoid bone ( J:44094 )

• at E18.5, the presphenoid bone is somewhat reduced

small temporal bone squamous part ( J:44094 )

• at E18.5, the squamosal bone is somewhat reduced

absent hyoid bone ( J:44094 )

• at E18.5, the main body of the hyoid bone including the greater horn, which originates from neural crest cells derived from r6-r7, is absent

absent stapes ( J:44094 )

• at E18.5, the stapes, which originates from neural crest cells derived from r3-r5, is absent

respiratory system

abnormal thyroid cartilage morphology ( J:44094 )

• at E18.5, the thyroid cartilage is consistently malformed

muscle

abnormal myotome development ( J:50279 )

• at E10.0, the length of dermomyotome in the mediolateral direction is reduced and the myotome layer is not clearly identifiable

• by E11.0, only small clusters of myotomal cells are observed instead of a condensed cell layer

• notably, expression of a myogenic gene, Myf5, is reduced at E9.5 but recovered at E11.0, indicating that early differentiation of myotomal cells is impaired

abnormal dermomyotome development ( J:50279 )

• at E9.5, double homozygotes show absence of medial dermomyotome formation caused by a loss of cells that normally form the medial lip, with no notable changes in cell proliferation or cell survival

• in addition, mediolateral patterning of the dermomyotome is defective and dermomyotome appears to be lateralized