Phenotypes associated with this allele

• Allele Symbol: Wnt1^tm1Brd
• Allele Name: targeted mutation 1, Allan Bradley
• Allele ID: MGI:1857490
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Wnt1^tm1Brd/Wnt1^tm1Brd	involves: 129S7/SvEvBrd * C57BL/6J	MGI:3639584
cx2	Wnt1^tm1Brd/Wnt1^tm1Brd Wnt3a^tm1Amc/Wnt3a^tm1Amc	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:2166755
cx3	Wnt1^tm1Brd/Wnt1^tm1Brd Wnt4^tm1Amc/Wnt4^tm1Amc	involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6J	MGI:3639722
cx4	Wnt1^tm1Brd/Wnt1^tm1Brd Wnt8a^tm1(KOMP)Vlcg/Wnt8a^tm1(KOMP)Vlcg	involves: 129S7/SvEvBrd * C57BL/6NTac	MGI:5471826

Genotype
MGI:3639584

hm1

• Allelic Composition: Wnt1^tm1Brd/Wnt1^tm1Brd
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

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

mortality/aging

neonatal lethality, complete penetrance ( J:10730 )

• homozygotes develop to term but die within 24 hrs of birth

nervous system

decreased rhombomere 1 size ( J:10730 )

• at E9.5, homozygotes display a shorter than normal metencephalic rhombomere-1 (r1)

abnormal midbrain development ( J:10730 )

• at E9.5, the caudal two-thirds of the midbrain fail to develop whereas the remaining (presumably rostral) one-third is present

• notably, most of the neural tube and all non-neural tissues appear normal

abnormal cranial flexure morphology ( J:10730 )

• at E16.5, homozygotes show an abnormal cranial flexure due to neural tissue loss; however, the thalamus and pons appear normal

abnormal midbrain-hindbrain boundary development ( J:10730 )

• at E9.5, a normal midbrain-metencephalic junction fails to develop

absent midbrain ( J:10730 )

• by E14.5, most, if not all, of the mutant midbrain is absent

abnormal forebrain morphology ( J:10730 )

• at E9.5, absence of primitive brain tissue moves the forebrain caudally, resulting in a novel juxtaposition of rostral midbrain with caudal metencephalon

abnormal metencephalon morphology ( J:10730 )

• at E9.5, homozygotes show absence of rostral metencephalic tissue

• at E14.5 and E16.5, dorsally-derived cerebellar tissue is absent whereas the ventrally-derived pons is present

absent cerebellum ( J:10730 )

• by E14.5, homozygotes lack an identifiable cerebellum; in contrast, the posterior choroid plexus is present, and the cerebral hemisphere, diencephalon, myelencephalon, and spinal cord appear normal

skeleton

abnormal parietal bone morphology ( J:44094 )

• at E18.5, homozygotes lack part of the parietal bone, a non-crest derivative

craniofacial

abnormal parietal bone morphology ( J:44094 )

• at E18.5, homozygotes lack part of the parietal bone, a non-crest derivative

hematopoietic system

decreased thymocyte number ( J:75999 )

• at E15-E16, homozygotes show a 20-30% reduction in thymocyte number relative to wild-type embryos

• however, T cell maturation during fetal development appears unaffected

immune system

decreased thymocyte number ( J:75999 )

• at E15-E16, homozygotes show a 20-30% reduction in thymocyte number relative to wild-type embryos

• however, T cell maturation during fetal development appears unaffected

embryo

decreased rhombomere 1 size ( J:10730 )

• at E9.5, homozygotes display a shorter than normal metencephalic rhombomere-1 (r1)

endocrine/exocrine glands

decreased thymocyte number ( J:75999 )

• at E15-E16, homozygotes show a 20-30% reduction in thymocyte number relative to wild-type embryos

• however, T cell maturation during fetal development appears unaffected

Genotype
MGI:2166755

cx2

• 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

Genotype
MGI:3639722

cx3

• Allelic Composition: Wnt1^tm1Brd/Wnt1^tm1Brd; Wnt4^tm1Amc/Wnt4^tm1Amc
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6J

hematopoietic system

decreased thymocyte number ( J:75999 )

• at E15-E16, double homozygotes show a 50-70% reduction of immature and mature thymocytes relative to wild-type embryos; this decrease is significantly greater than that observed in either single homozygote (20-30%)

immune system

decreased thymocyte number ( J:75999 )

• at E15-E16, double homozygotes show a 50-70% reduction of immature and mature thymocytes relative to wild-type embryos; this decrease is significantly greater than that observed in either single homozygote (20-30%)

endocrine/exocrine glands

decreased thymocyte number ( J:75999 )

• at E15-E16, double homozygotes show a 50-70% reduction of immature and mature thymocytes relative to wild-type embryos; this decrease is significantly greater than that observed in either single homozygote (20-30%)

Genotype
MGI:5471826

cx4

• Allelic Composition: Wnt1^tm1Brd/Wnt1^tm1Brd; Wnt8a^{tm1(KOMP)Vlcg}/Wnt8a^{tm1(KOMP)Vlcg}
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6NTac

hearing/vestibular/ear

abnormal endolymphatic duct morphology ( J:194132 )

• reduced endolymphatic sac at the dorsal portion of the endolymphatic duct at E15.5