Phenotypes associated with this allele

• Allele Symbol: Chuk^tm1Ver
• Allele Name: targeted mutation 1, Inder M Verma
• Allele ID: MGI:2386272
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Chuk^tm1Ver/Chuk^tm1Ver	involves: 129S4/SvJae * C57BL/6J	MGI:3609426
cx2	Chuk^tm1Ver/Chuk^tm1Ver Ikbkb^tm1Ver/Ikbkb^tm1Ver Tnfrsf1a^tm1Mak/Tnfrsf1a^tm1Mak	involves: 129/Sv * 129S4/SvJae * C57BL/6J	MGI:3609629
cx3	Chuk^tm1Ver/Chuk^tm1Ver Tnfrsf1a^tm1Mak/Tnfrsf1a^tm1Mak	involves: 129/Sv * 129S4/SvJae * C57BL/6J	MGI:3609632
cx4	Chuk^tm1Ver/Chuk^tm1Ver Ikbkb^tm1Ver/Ikbkb^tm1Ver	involves: 129S4/SvJae * C57BL/6J	MGI:3609628

Genotype
MGI:3609426

hm1

• Allelic Composition: Chuk^tm1Ver/Chuk^tm1Ver
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

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

mortality/aging

neonatal lethality, complete penetrance ( J:55415 )

• although homozygotes develop to term, they are stillborn or die shortly after birth

limbs/digits/tail

abnormal limb morphology ( J:55415 )

• at birth, all long bones of mutant limbs appear to be formed with no major defects in the pattern and size of proximal limb elements; in contrast, the curvature of distal limb elements is abnormal

• in mutants, upper limb (humerus) and middle limb elements (radius, and ulna) fail to emerge out of the body trunk, resuting in a bottle-shaped body morphology

abnormal limb bud morphology ( J:55415 )

• as early as E12.5, mutant limb buds are short and dumpy

abnormal phalanx morphology ( J:55415 )

• in newborn homozygotes, most distal limb elements exhibit retarded and aberrant phalanx formation

abnormal hindlimb morphology ( J:55415 )

• at birth, mutant hindlimbs together with the curled tail are embedded in thick skin

short limbs ( J:55415 )

• at birth, all four mutant limbs are barely protruding and appear to be shortened

curly tail ( J:55415 )

• as early as E12.5, homozygotes exhibit a curled, fused tail

skeleton

abnormal craniofacial bone morphology ( J:55415 )

• newborn homozygotes exibit abnormal craniofacial bone morphology

abnormal incisor morphology ( J:55415 )

• newborn homozygotes exhibit smaller and distorted incisors

small incisors ( J:55415 )

abnormal phalanx morphology ( J:55415 )

• in newborn homozygotes, most distal limb elements exhibit retarded and aberrant phalanx formation

abnormal sternebra morphology ( J:55415 )

• homozygotes have a broader sternum exhibiting incomplete and asymmetric ossification with split sternebra 6

• mutant sternal bands are shorter and broader with an abnormal kinked shape but remain well fused and functional

asymmetric sternocostal joints ( J:55415 )

• mutant ribs display a kinky fusion to the sternum

wide sternum ( J:55415 )

abnormal sternum ossification ( J:55415 )

• incomplete and asymmetric ossification

craniofacial

abnormal craniofacial bone morphology ( J:55415 )

• newborn homozygotes exibit abnormal craniofacial bone morphology

abnormal incisor morphology ( J:55415 )

• newborn homozygotes exhibit smaller and distorted incisors

small incisors ( J:55415 )

palatal shelves fail to meet at midline ( J:55415 )

• mutant bilateral palate shelves remain unfused, allowing the more dorsal lying vomer and presphenoid to be exposed

cleft secondary palate ( J:55415 )

• newborn homozygotes exhibit a cleft secondary palate

digestive/alimentary system

palatal shelves fail to meet at midline ( J:55415 )

• mutant bilateral palate shelves remain unfused, allowing the more dorsal lying vomer and presphenoid to be exposed

cleft secondary palate ( J:55415 )

• newborn homozygotes exhibit a cleft secondary palate

abnormal intestine morphology ( J:55415 )

• newborn homozygotes display a shorter and narrower intestine than wild-type mice

small stomach ( J:55415 )

• newborn homozygotes have a significantly smaller stomach than wild-type newborns

liver/biliary system

dilated gallbladder ( J:55415 )

• all newborn homozygotes display an expanded bladder

embryo

abnormal embryonic tissue morphology ( J:55415 )

abnormal limb bud morphology ( J:55415 )

• as early as E12.5, mutant limb buds are short and dumpy

homeostasis/metabolism

impaired skin barrier function ( J:55415 )

cellular

abnormal cell physiology ( J:55415 )

• mutant MEFs exhibit significantly reduced NF-kappaB activation upon induction with TNF or IL-1

abnormal keratinocyte differentiation ( J:55415 )

growth/size/body

abnormal incisor morphology ( J:55415 )

• newborn homozygotes exhibit smaller and distorted incisors

small incisors ( J:55415 )

palatal shelves fail to meet at midline ( J:55415 )

• mutant bilateral palate shelves remain unfused, allowing the more dorsal lying vomer and presphenoid to be exposed

cleft secondary palate ( J:55415 )

• newborn homozygotes exhibit a cleft secondary palate

omphalocele ( J:55415 )

• at E18, homozygotes exhibit retarded umbilical hernia withdrawal relative to wild-type mice

endocrine/exocrine glands

dilated gallbladder ( J:55415 )

• all newborn homozygotes display an expanded bladder

integument

impaired skin barrier function ( J:55415 )

abnormal hair follicle morphology ( J:55415 )

• newborn homozygotes display a reduced number of hair follicles, as mutant follicles fail to invaginate deeply into dermis

absent vibrissae ( J:55415 )

abnormal epidermal layer morphology ( J:55415 )

• the epidermis of newborn homozygotes displays a block in stratum corneum differentiation and complete absence of squames

abnormal keratinocyte differentiation ( J:55415 )

absent epidermis stratum corneum ( J:55415 )

abnormal epidermis stratum granulosum morphology ( J:55415 )

• newborn homozygotes lack identifiable epidermal granular cells with distinctive keratohyalin granules; instead, several layers of flattened cells are present on the surface of mutant skin

abnormal epidermis suprabasal layer morphology ( J:55415 )

• newborn homozygotes exhibit significantly increased suprabasal cell density relative to wild-type mice

• mutant suprabasal cells fail to differentiate into granular cells and cornified cells, as shown by significantly reduced expression of filaggrin and loricrin in mutant skin

epidermal desquamation ( J:55415 )

• newborn homozygotes exhibit absence of the superficial keratinized squamous layer of the epidermis

abnormal skin appearance ( J:55415 )

• newborn homozygotes have an abnormally tense and sticky skin that fails to attach to the limbs and thus covers the body like a bag

shiny skin ( J:55415 )

translucent skin ( J:55415 )

thick skin ( J:55415 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
fetal encasement syndrome		DOID:0060647	OMIM:613630	J:195185

Genotype
MGI:3609629

cx2

• Allelic Composition: Chuk^tm1Ver/Chuk^tm1Ver; Ikbkb^tm1Ver/Ikbkb^tm1Ver; Tnfrsf1a^tm1Mak/Tnfrsf1a^tm1Mak
• Genetic Background: involves: 129/Sv * 129S4/SvJae * C57BL/6J

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:63443 )

• triple homozygotes survive to ~E16.5, exhibiting a morphology similar to that observed in Chuk^tm1Ver mutant embryos

limbs/digits/tail

broad limb buds ( J:63443 )

• at E14.5, triple homozygotes exhibit dumpy limb buds, similar to those observed in Chuk^tm1Ver mutant embryos

curly tail ( J:63443 )

• at E14.5, triple homozygotes exhibit curled tails, similar to those observed in Chuk^tm1Ver mutant embryos

nervous system

open neural tube ( J:63443 )

• at E14.5, triple homozygotes exhibit a neural tube defect, similar to that observed in mice doubly homozygous for Chuk^tm1Ver and Ikbkb^tm1Ver

embryo

broad limb buds ( J:63443 )

• at E14.5, triple homozygotes exhibit dumpy limb buds, similar to those observed in Chuk^tm1Ver mutant embryos

open neural tube ( J:63443 )

• at E14.5, triple homozygotes exhibit a neural tube defect, similar to that observed in mice doubly homozygous for Chuk^tm1Ver and Ikbkb^tm1Ver

Genotype
MGI:3609632

cx3

• Allelic Composition: Chuk^tm1Ver/Chuk^tm1Ver; Tnfrsf1a^tm1Mak/Tnfrsf1a^tm1Mak
• Genetic Background: involves: 129/Sv * 129S4/SvJae * C57BL/6J

limbs/digits/tail

broad limb buds ( J:63443 )

• at E14.5, double homozygotes exhibit dumpy limb buds, similar to those observed in Chuk^tm1Ver mutant embryos

curly tail ( J:63443 )

• at E14.5, double homozygotes exhibit curled tails, similar to those observed in Chuk^tm1Ver mutant embryos

embryo

broad limb buds ( J:63443 )

• at E14.5, double homozygotes exhibit dumpy limb buds, similar to those observed in Chuk^tm1Ver mutant embryos

Genotype
MGI:3609628

cx4

• Allelic Composition: Chuk^tm1Ver/Chuk^tm1Ver; Ikbkb^tm1Ver/Ikbkb^tm1Ver
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:63443 )

• double mutant embryos are obtained at the expected frequency at E11.5, but die at E12 as a result of liver dysfunction

liver/biliary system

increased hepatocyte apoptosis ( J:63443 )

• at E11.5-E12, double homozygotes exhibit a massive increase in liver apoptosis relative to wild-type embryos, indicating liver dysfunction

liver degeneration ( J:63443 )

nervous system

increased hindbrain apoptosis ( J:63443 )

• at E9.5, increased apoptosis is noted in the neuroepithelium of double mutant hindbrain

increased embryonic neuroepithelium apoptosis ( J:63443 )

• at E9.5, double homozygous mutant embryos show increased apoptosis in the neuronal epithelium at the hindbrain level

• however, no defects in neural differentiation are observed

increased spinal cord apoptosis ( J:63443 )

• at ~E11.5-E12, double homozygotes exhibit a 2-fold increase in apoptosis in the spinal cord relative to wild-type mice

open neural tube ( J:63443 )

• ~70% of double homozygotes fail to close the neural tube in the hindbrain

small embryonic telencephalon ( J:63443 )

• double mutant embryos exhibit reduced telencephalic vesicles relative to wild-type embryos

abnormal hindbrain morphology ( J:63443 )

• at E9.5, double homozygotes lack the roof of hindbrain

abnormal dorsal root ganglion morphology ( J:63443 )

• at about E11.5-E12, double homozygotes exhibit a 2-fold increase in apoptosis in dorsal root ganglia relative to wild-type mice

cellular

abnormal cell physiology ( J:63443 )

• double mutant MEFs exhibit no detectable NF-kappaB DNA binding activity upon induction with human TNF, IL-1alpha, or LPS

• notably, NF-kappaB activation is more attenuated in single Ikbkb^tm1Ver mutant MEFs than in single Chuk^tm1Ver mutant MEFs

increased hindbrain apoptosis ( J:63443 )

• at E9.5, increased apoptosis is noted in the neuroepithelium of double mutant hindbrain

increased hepatocyte apoptosis ( J:63443 )

• at E11.5-E12, double homozygotes exhibit a massive increase in liver apoptosis relative to wild-type embryos, indicating liver dysfunction

increased embryonic neuroepithelium apoptosis ( J:63443 )

• at E9.5, double homozygous mutant embryos show increased apoptosis in the neuronal epithelium at the hindbrain level

• however, no defects in neural differentiation are observed

increased spinal cord apoptosis ( J:63443 )

• at ~E11.5-E12, double homozygotes exhibit a 2-fold increase in apoptosis in the spinal cord relative to wild-type mice

embryo

abnormal neural fold elevation formation ( J:63443 )

• at E9.5, double homozygotes exhibit defective neurulation: neural folds at the hindbrain level fail to elevate on either side of the midline and do not bend toward each other

open neural tube ( J:63443 )

• ~70% of double homozygotes fail to close the neural tube in the hindbrain