Phenotypes associated with this allele

• Allele Symbol: Ext2^tm1Werb
• Allele Name: targeted mutation 1, Zena Werb
• Allele ID: MGI:3608690
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ext2^tm1Werb/Ext2^tm1Werb	involves: C57BL/6	MGI:3608783
ht2	Ext2^tm1Werb/Ext2^+	involves: C57BL/6	MGI:3608784
cx3	Ext2^tm1Werb/Ext2^+ Sulf2^Gt(XST155)Byg/Sulf2^Gt(XST155)Byg	involves: 129P2/OlaHsd * C57BL/6	MGI:3699302

Genotype
MGI:3608783

hm1

• Allelic Composition: Ext2^tm1Werb/Ext2^tm1Werb
• Genetic Background: involves: C57BL/6

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

mortality/aging

embryonic lethality between implantation and somite formation, complete penetrance ( J:103125 )

• brachyury is absent in E6.5 homozygotes but present at E7.5 in class 2 and class 3 homozygotes

• at E6.5 ectoplacental cone formation appears normal, but extra-embryonic regions are underdeveloped and the egg cylinder does not elongate

embryo

failure to gastrulate ( J:103125 )

abnormal egg cylinder morphology ( J:103125 )

• ectoplacental cone forms but extra-embryonic regions are underdeveloped and the egg cylinder elongation is deficient to varying degrees

absent mesoderm ( J:103125 )

• at E7.5 25% of homozygotes, designated class 1, have a round-shaped egg cylinder, consisting of only ectoderm and visceral endoderm with no primitive streak or mesoderm, seeming to be directly connected to the ectoplacental cone, with increased apoptosis in the ectoderal layer, and no extra-embryonic ectoderm, endoderm, or mesoderm

• at E7.5 50% of homozygotes, designated class 2, have an egg cylinder elongated to about one-third normal size but only consisting of embryonic ectoderm and visceral endoderm, and develop immature extra-embryonic ectoderm and endoderm but lack extra-embryonic mesoderm

• at E7.5 the remaining homozygotes, designated class 3, have further elongation of the embryonic and extra-embryonic regions but lack embryonic and extra-embryonic mesoderm and initiation of a head fold with the presence of neuroectoderm is found

failure of primitive streak formation ( J:103125 )

• the formation of the primitive streak is initiated, but fails to properly form mesoderm

skeleton

abnormal skeleton morphology ( J:103125 )

• heparan sulfate is not produced

Genotype
MGI:3608784

ht2

• Allelic Composition: Ext2^tm1Werb/Ext2⁺
• Genetic Background: involves: C57BL/6

skeleton

skeleton phenotype ( J:103125 )

N

exostosis ( J:103125 )

• although bone length is normal, 28% of heterozygotes have exostoses on the ribs, but not on the long bones, which are located near the costochondral junction and are composed of cortical and medullary bone with an overlying hyaline cartilage cap

• at E18.5 there are no morphological abnormalities in the unla, radius, or femur and mineralization of the cartilage matrix, formation of the bony collar surrounding the hypertrophic chondrocytes and formation of the trabecular bone appear normal

abnormal cartilage morphology ( J:103125 )

• each rib has nodules or single misplaced chondrocytes with overlying perichondrium

• although chondrocytes do produce heparan sulfate and no aberrant hedgehog activity is found in the chondrocytes, chondrocytes in the proliferative zone of E18.5 ulnae lack columnar organization

abnormal skeleton development ( J:103125 )

abnormal bone ossification ( J:103125 )

• the expression domains of Pthr1 and Ihh in E18.5 ulnae growth plates are slightly smaller than normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hereditary multiple exostoses		DOID:206	OMIM:133700 OMIM:133701 OMIM:600209	J:103125

Genotype
MGI:3699302

cx3

• Allelic Composition: Ext2^tm1Werb/Ext2⁺; Sulf2^{Gt(XST155)Byg}/Sulf2^{Gt(XST155)Byg}
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

prenatal lethality, incomplete penetrance ( J:117689 )

• numbers of homozygotes produced is reduced by ~30% from expected numbers; no age when loss occurs is indicated