Phenotypes associated with this allele

• Allele Symbol: Cdkn1c^tm1Bbd
• Allele Name: targeted mutation 1, Mariano Barbacid
• Allele ID: MGI:1933757
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cdkn1c^tm1Bbd/Cdkn1c^tm1Bbd	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:2175762
hm2	Cdkn1c^tm1Bbd/Cdkn1c^tm1Bbd	involves: 129S1/Sv * 129X1/SvJ * ICR	MGI:2175764
ht3	Cdkn1c^tm1Bbd/Cdkn1c^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3712850

Genotype
MGI:2175762

hm1

• Allelic Composition: Cdkn1c^tm1Bbd/Cdkn1c^tm1Bbd
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

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

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:40142 )

• slight lethality between E10.5 and E16.5

neonatal lethality, incomplete penetrance ( J:40142 )

• most homozygotes die within a few hours of birth

• about 10.6% of homozygotes born alive are morphologically and behaviorally normal and survive into adulthood

behavior/neurological

absent gastric milk in neonates ( J:40142 )

abnormal suckling behavior ( J:40142 )

• difficulty suckling as determined by absence of milk in the stomach

skeleton

abnormal long bone epiphysis morphology ( J:40142 )

• higher density of chondrocytes

abnormal bone ossification ( J:40142 )

• delayed terminal differentiation of chondrocytes in endochondral bone

delayed endochondral bone ossification ( J:40142 )

craniofacial

palatal shelves fail to meet at midline ( J:40142 )

• failure of palatal shelves to grow and meet at the midline, possibly due to apoptotic cells

• at E14.5, mutants show increased apoptosis of epithelial cells on the surface of the palatal shelves and in the mesenchyme located at the base of the palatal shelves

abnormal hard palate morphology ( J:40142 )

abnormal soft palate morphology ( J:40142 )

cleft palate ( J:40142 )

• observed in about half of live births

digestive/alimentary system

palatal shelves fail to meet at midline ( J:40142 )

• failure of palatal shelves to grow and meet at the midline, possibly due to apoptotic cells

• at E14.5, mutants show increased apoptosis of epithelial cells on the surface of the palatal shelves and in the mesenchyme located at the base of the palatal shelves

abnormal hard palate morphology ( J:40142 )

abnormal soft palate morphology ( J:40142 )

cleft palate ( J:40142 )

• observed in about half of live births

abnormal digestive system development ( J:40142 )

• increased apoptosis in the smooth muscle layer of the intestine

abnormal intestine morphology ( J:40142 )

• about half of live births with inflated gastrointestinal tract

• 40% of live births with grossly shortened intestinal tract, independent of presence or absence of cleft palate

abnormal duodenum morphology ( J:40142 )

• may end blindly and open to the abdominal cavity

abnormal ileum morphology ( J:40142 )

• at least partially absent in mice that die in the first day of life

• distal end may be open to the abdominal cavity

absent jejunum ( J:40142 )

• often absent in mice that die in the first day of life

meteorism ( J:40142 )

• in half of animals born live, an inflated gastrointestinal tract is seen

nervous system

increased midbrain apoptosis ( J:88146 )

• apoptotic cell death in the ventral midbrain is increased 2 fold at E18.5

abnormal midbrain morphology ( J:88146 )

• tyrosine hydroxylase is reduced in the ventral midbrain at E18.5

limbs/digits/tail

short limbs ( J:40142 )

• short limbs at birth in those mice that die early

growth/size/body

palatal shelves fail to meet at midline ( J:40142 )

• failure of palatal shelves to grow and meet at the midline, possibly due to apoptotic cells

• at E14.5, mutants show increased apoptosis of epithelial cells on the surface of the palatal shelves and in the mesenchyme located at the base of the palatal shelves

abnormal hard palate morphology ( J:40142 )

abnormal soft palate morphology ( J:40142 )

cleft palate ( J:40142 )

• observed in about half of live births

meteorism ( J:40142 )

• in half of animals born live, an inflated gastrointestinal tract is seen

cellular

increased midbrain apoptosis ( J:88146 )

• apoptotic cell death in the ventral midbrain is increased 2 fold at E18.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	Beckwith-Wiedemann syndrome	DOID:5572	OMIM:130650	J:40142

Genotype
MGI:2175764

hm2

• Allelic Composition: Cdkn1c^tm1Bbd/Cdkn1c^tm1Bbd
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * ICR

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:40142 )

• slight lethality between E10.5 and E16.5

neonatal lethality, incomplete penetrance ( J:40142 )

• most homozygotes die within a few hours of birth

• about 10.6% of homozygotes born alive are morphologically and behaviorally normal and survive into adulthood

craniofacial

abnormal craniofacial bone morphology ( J:40142 )

skeleton

abnormal craniofacial bone morphology ( J:40142 )

abnormal limb bone morphology ( J:40142 )

abnormal skeleton development ( J:40142 )

digestive/alimentary system

abnormal digestive system morphology ( J:40142 )

limbs/digits/tail

abnormal limb bone morphology ( J:40142 )

Genotype
MGI:3712850

ht3

• Allelic Composition: Cdkn1c^tm1Bbd/Cdkn1c⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:40142 )

• slight lethality between E10.5 and E16.5

neonatal lethality, incomplete penetrance ( J:40142 )

• about half of heterozygotes die within a few hours of birth

• about 5% of mice survive to adulthood

behavior/neurological

absent gastric milk in neonates ( J:40142 )

• absence of milk spots in the stomach of mice that die early

abnormal suckling behavior ( J:40142 )

• difficulty suckling as determined by absence of milk in the stomach in those mice that die early

craniofacial

cleft palate ( J:40142 )

• observed in those mice that die early

digestive/alimentary system

cleft palate ( J:40142 )

• observed in those mice that die early

abnormal intestine morphology ( J:40142 )

• various intestinal abnormalities in those mice that die early

limbs/digits/tail

short limbs ( J:40142 )

• short limbs at birth in those mice that die early

cellular

paternal imprinting ( J:40142 )

• paternal allele is transcriptionally repressed

• no abnormal phenotype in crosses between heterozygous males and wild-type females

• abnormal phenotype seen in crosses between heterozygous females and normal males similar to that seen for homozygous mutants

growth/size/body

cleft palate ( J:40142 )

• observed in those mice that die early