Phenotypes associated with this allele

• Allele Symbol: Cdkn1c^tm1Kat
• Allele Name: targeted mutation 1, Katsuhiko Takahashi
• Allele ID: MGI:1933758
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cdkn1c^tm1Kat/Cdkn1c^tm1Kat	involves: 129P2/OlaHsd	MGI:3838162
hm2	Cdkn1c^tm1Kat/Cdkn1c^tm1Kat	involves: 129P2/OlaHsd * C57BL/6	MGI:2175766
ht3	Cdkn1c^tm1Kat/Cdkn1c^+	involves: 129P2/OlaHsd	MGI:3838163
ht4	Cdkn1c^tm1Kat/Cdkn1c^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3712981
ht5	Cdkn1c^tm1Kat/Cdkn1c^+	involves: 129P2/OlaHsd * C57BL/6J	MGI:3840689

Genotype
MGI:3838162

hm1

• Allelic Composition: Cdkn1c^tm1Kat/Cdkn1c^tm1Kat
• Genetic Background: involves: 129P2/OlaHsd

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

renal/urinary system

increased urine protein level ( J:102331 )

• by day 17.5 of pregnancy, protein secretion is 5 times greater than in pregnant wild-type mice

• however, after deliver protein secretion is normal

abnormal renal glomerulus morphology ( J:102331 )

• glomeruli are enlarged and irregularly shaped with increased subendothelial and mesangial depositions in glomeruli capillaries by day 17.5 of pregnancy unlike in pregnant wild-type mice

cortical renal glomerulopathies ( J:102331 )

• some pregnant mice exhibit nephrosclerosis unlike pregnant wild-type mice

abnormal renal tubule morphology ( J:102331 )

• fibroid and hyaline deposits are observed in the proximal and distal tubules of pregnant mice unlike in pregnant wild-type mice

embryo

abnormal trophoblast giant cell morphology ( J:102331 )

• fewer giant cells invade to maternal vessels at the maternal-fetal interface compared to in wild-type mice

abnormal placenta labyrinth morphology ( J:102331 )

• the labyrinthine space is narrow unlike in wild-type mice due to increased proliferation of spongio- and labyrinthine trophoblasts

increased placenta weight ( J:102331 )

cardiovascular system

increased systemic arterial systolic blood pressure ( J:102331 )

• systolic blood pressure increases at E9.5 through delivery before retuning to normal unlike pregnant wild-type mice that maintain normal blood pressure throughout pregnancy

• however, after delivery mice exhibit normal blood pressure

hematopoietic system

thrombocytopenia ( J:102331 )

• platelet counts are decreased to 48% of counts in pregnant wild-type by day 17 of pregnancy

homeostasis/metabolism

increased urine protein level ( J:102331 )

• by day 17.5 of pregnancy, protein secretion is 5 times greater than in pregnant wild-type mice

• however, after deliver protein secretion is normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pre-eclampsia		DOID:10591	OMIM:189800 OMIM:609402 OMIM:609403 OMIM:609404 OMIM:614592	J:102331

Genotype
MGI:2175766

hm2

• Allelic Composition: Cdkn1c^tm1Kat/Cdkn1c^tm1Kat
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:61190 )

• slight lethality before birth

neonatal lethality, incomplete penetrance ( J:61190 )

• most homozygotes die within 24 hours of birth

postnatal lethality, incomplete penetrance ( J:61190 )

• most mutant mice exhibit early postnatal lethality

• about 10% of homozygotes survive beyond weaning; these do not exhibit cleft palate nor intestinal abnormalities

behavior/neurological

absent gastric milk in neonates ( J:61190 )

dysphagia ( J:61190 )

• suggested by empty stomachs

respiratory system

respiratory distress ( J:61190 )

• severe

homeostasis/metabolism

cyanosis ( J:61190 )

• severe

craniofacial

cleft secondary palate ( J:61190 )

• observed in those mice that die early

digestive/alimentary system

dysphagia ( J:61190 )

• suggested by empty stomachs

cleft secondary palate ( J:61190 )

• observed in those mice that die early

abnormal intestine morphology ( J:61190 )

• inflated abdomen due to air bubbles in the gastrointestinal tract

• markedly shortened intestine with coagulated blood

meteorism ( J:61190 )

• inflated abdomen with massive air bubbles in the gastrointestinal tract

skeleton

abnormal humerus morphology ( J:61190 )

• ossified parts of the humerus are shorter than normal

abnormal endochondral bone ossification ( J:61190 )

• defective endochondral bone ossification

abnormal intramembranous bone ossification ( J:61190 )

• ossification of membranous bone in the cranium partially impaired

growth/size/body

cleft secondary palate ( J:61190 )

• observed in those mice that die early

meteorism ( J:61190 )

• inflated abdomen with massive air bubbles in the gastrointestinal tract

decreased body size ( J:61190 )

• much smaller body size

decreased body weight ( J:61190 )

• 1/4 to 1/2 normal body weight

reproductive system

abnormal female reproductive system morphology ( J:61190 )

♀

increased atretic ovarian follicle number ( J:61190 )

♀ • increased numbers of atretic follicles

abnormal uterus development ( J:61190 )

♀ • immature at 5 weeks of age

hydrometra ( J:61190 )

♀ • fluid in uterus at 5 months of age

vagina atresia ( J:61190 )

♀ • vaginal atresia at 5 months of age

abnormal male reproductive system morphology ( J:61190 )

♂ • delayed maturation

abnormal prostate gland development ( J:61190 )

♂ • immature at 5 weeks of age

abnormal seminal vesicle development ( J:61190 )

♂ • immature at 5 weeks of age

abnormal testis development ( J:61190 )

♂ • immature at 5 weeks of age

delayed sexual maturation ( J:61190 )

♂ • delayed sexual maturation in males

abnormal fertility/fecundity ( J:61190 )

female infertility ( J:61190 )

♀ • sterile

embryo

abnormal trophoblast giant cell morphology ( J:102331 )

• reduced invasion of giant cells

abnormal spongiotrophoblast layer morphology ( J:102331 , J:102344 )

• increased proliferation of spongiotrophoblasts (J:102344)

abnormal placenta labyrinth morphology ( J:102331 , J:102344 )

• increased proliferation of labyrinthine trophoblasts (J:102344)

• reduced labyrinthine space (J:102344)

enlarged placenta ( J:102344 )

• placentomegaly

increased placenta weight ( J:102331 )

• 140mg at E17.5 compared to 110mg for controls

immune system

abnormal spleen white pulp morphology ( J:61190 )

• underdeveloped

endocrine/exocrine glands

abnormal gland morphology ( J:61190 )

abnormal prostate gland development ( J:61190 )

♂ • immature at 5 weeks of age

abnormal seminal vesicle development ( J:61190 )

♂ • immature at 5 weeks of age

increased atretic ovarian follicle number ( J:61190 )

♀ • increased numbers of atretic follicles

abnormal testis development ( J:61190 )

♂ • immature at 5 weeks of age

limbs/digits/tail

abnormal humerus morphology ( J:61190 )

• ossified parts of the humerus are shorter than normal

hematopoietic system

abnormal spleen white pulp morphology ( J:61190 )

• underdeveloped

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	Beckwith-Wiedemann syndrome	DOID:5572	OMIM:130650	J:61190

Genotype
MGI:3838163

ht3

• Allelic Composition: Cdkn1c^tm1Kat/Cdkn1c⁺
• Genetic Background: involves: 129P2/OlaHsd

renal/urinary system

increased urine protein level ( J:102331 )

• when this allele is maternally inherited, protein secretion is 2.8 times greater by day 17.5 of pregnancy than in pregnant wild-type mice

• however, protein secretion is normal after delivery or when this allele is inherited parentally

abnormal renal glomerulus morphology ( J:102331 )

• when this allele is maternally inherited, glomeruli are enlarged and irregularly shaped with increased subendothelial and mesangial depositions in glomeruli capillaries by day 17.5 of pregnancy unlike in pregnant wild-type mice

cortical renal glomerulopathies ( J:102331 )

• when this allele is maternally inherited, some pregnant mice exhibit nephrosclerosis unlike pregnant wild-type mice

abnormal renal tubule morphology ( J:102331 )

• when this allele is maternally inherited, fibroid and hyaline deposits are observed in the proximal and distal tubules of pregnant mice unlike in pregnant wild-type mice

embryo

abnormal trophoblast giant cell morphology ( J:102331 )

• when this allele is maternally inherited, fewer giant cells invade to maternal vessels at the maternal-fetal interface compared to in wild-type mice

abnormal placenta labyrinth morphology ( J:102331 )

• when this allele is maternally inherited, the labyrinthine space is narrow unlike in wild-type mice due to increased proliferation of spongio- and labyrinthine trophoblasts

increased placenta weight ( J:102331 )

• when this allele is maternally inherited

cardiovascular system

increased systemic arterial systolic blood pressure ( J:102331 )

• when this allele is maternally inherited, systolic blood pressure increases at E9.5 through delivery before retuning to normal unlike pregnant wild-type mice that maintain normal blood pressure throughout pregnancy

• however, blood pressure is normal after delivery or when this allele is inherited parentally

hematopoietic system

thrombocytopenia ( J:102331 )

• when this allele is maternally inherited, platelet counts are decreased to 55% of counts in pregnant wild-type by day 17 of pregnancy

• however, platelet counts are normal when this allele is inherited parentally

homeostasis/metabolism

increased urine protein level ( J:102331 )

• when this allele is maternally inherited, protein secretion is 2.8 times greater by day 17.5 of pregnancy than in pregnant wild-type mice

• however, protein secretion is normal after delivery or when this allele is inherited parentally

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pre-eclampsia		DOID:10591	OMIM:189800 OMIM:609402 OMIM:609403 OMIM:609404 OMIM:614592	J:102331

Genotype
MGI:3712981

ht4

• Allelic Composition: Cdkn1c^tm1Kat/Cdkn1c⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:61190 )

• slight lethality before birth

neonatal lethality, incomplete penetrance ( J:61190 )

• about half of heterozygotes die within 24 hours of birth

behavior/neurological

dysphagia ( J:61190 )

• in about half of heterozygotes

• suggested by empty stomachs

respiratory system

respiratory distress ( J:61190 )

• in about half of heterozygotes

homeostasis/metabolism

cyanosis ( J:61190 )

• in about half of heterozygotes

increased urine protein level ( J:102331 )

• increases greatly in females during pregnancy

craniofacial

cleft secondary palate ( J:61190 )

• observed in those mice that die early

digestive/alimentary system

dysphagia ( J:61190 )

• in about half of heterozygotes

• suggested by empty stomachs

cleft secondary palate ( J:61190 )

• observed in those mice that die early

abnormal intestine morphology ( J:61190 )

• various intestinal abnormalities in those mice that die early

reproductive system

short gestation period ( J:61190 )

♀ • birth 2 days early, after 18 days

hematopoietic system

thrombocytopenia ( J:102331 )

• in females during pregnancy, by 48-55%

cardiovascular system

increased systemic arterial blood pressure ( J:102331 )

• blood pressure rises during pregnancy

renal/urinary system

increased urine protein level ( J:102331 )

• increases greatly in females during pregnancy

abnormal kidney morphology ( J:102331 )

• endotheliosis leading to nephrosclerosis in pregnant females

abnormal renal glomerulus morphology ( J:102331 )

• enlarged in pregnant females at E17.5

• also irregularly shaped

cellular

paternal imprinting ( J:61190 )

• paternal allele is transcriptionally repressed

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

growth/size/body

cleft secondary palate ( J:61190 )

• observed in those mice that die early

Genotype
MGI:3840689

ht5

• Allelic Composition: Cdkn1c^tm1Kat/Cdkn1c⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

Small size of Cdkn1c^tm1Kat/Cdkn1c⁺ mice at 7 weeks of age

mortality/aging

neonatal lethality, incomplete penetrance ( J:147145 )

• most mice die shortly after birth although some survive to weaning

cellular

paternal imprinting ( J:147145 )

• all mice carry a maternally inherited mutant allele

embryo

embryonic growth retardation ( J:147145 )

abnormal placenta morphology ( J:147145 )

• dysplasia

growth/size/body

cleft palate ( J:147145 )

embryonic growth retardation ( J:147145 )

abnormal abdominal wall morphology ( J:147145 )

• thinning of the abdominal wall or omphalocele are seen

omphalocele ( J:147145 )

• thinning of the abdominal wall or omphalocele are seen

postnatal growth retardation ( J:147145 )

• seen in mice that survive to weaning

renal/urinary system

abnormal kidney papilla morphology ( J:147145 )

• dysplasia

digestive/alimentary system

cleft palate ( J:147145 )

abnormal intestine morphology ( J:147145 )

• short intestines

endocrine/exocrine glands

enlarged adrenal glands ( J:147145 )

vision/eye

abnormal lens development ( J:147145 )

• increased cell proliferation is seen in the lens at E13.5

cataract ( J:147145 )

reproductive system

uterus atrophy ( J:147145 )

♀

uterus atresia ( J:147145 )

♀

skeleton

abnormal long bone epiphyseal plate morphology ( J:147145 )

• increased cell proliferation is seen in the zones of proliferation and flattened cells in the humerus at E16.5

decreased length of long bones ( J:147145 )

abnormal rib morphology ( J:147145 )

abnormal vertebrae morphology ( J:147145 )

delayed bone ossification ( J:147145 )

• of the occipital bone, digits, and long bones

craniofacial

cleft palate ( J:147145 )