Phenotypes associated with this allele

• Allele Symbol: Chuk^tm1Mpa
• Allele Name: targeted mutation 1, Manolis Pasparakis
• Allele ID: MGI:3714160
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Chuk^tm1Mpa/Chuk^tm1Mpa Tg(KRT14-cre)1Cgn/?	involves: C57BL/6	MGI:3714173
cn2	Chuk^tm1Mpa/Chuk^tm1Mpa Ikbkb^tm2Cgn/Ikbkb^tm2Cgn Tg(Alb1-cre)7Gsc/0	involves: C57BL/6 * FVB/N	MGI:3804036

Genotype
MGI:3714173

cn1

• Allelic Composition: Chuk^tm1Mpa/Chuk^tm1Mpa; Tg(KRT14-cre)1Cgn/?
• Genetic Background: involves: C57BL/6

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

mortality/aging

neonatal lethality, complete penetrance ( J:122320 )

• pups die within a few hours of birth

homeostasis/metabolism

decreased circulating free fatty acids level ( J:122320 )

• free fatty acids and ceramide content are decreased in the outer layer of the epidermis

impaired skin barrier function ( J:122320 )

• skin on the limbs, tail and parts of the head show increased permeability

• however, skin on the body does not show increased permeability

increased cholesterol level ( J:122320 )

• cholesterol levels are mildly increased in the outer layer of the epidermis

growth/size/body

weight loss ( J:122320 )

• mice loose as much as 5% of their weight within 3 hours of birth

skeleton

skeleton phenotype ( J:122320 )

N • in contrast to Chuk^tm1.1Mpa homozygotes, mice do not have any skeletal abnormalities

integument

impaired skin barrier function ( J:122320 )

• skin on the limbs, tail and parts of the head show increased permeability

• however, skin on the body does not show increased permeability

abnormal skin morphology ( J:122320 )

• epidermis had increased vascularisation

• blood vessel diameter is increased within the epidermis

abnormal keratinocyte differentiation ( J:122320 )

• primary keratinocytes do not differentiate in medium with increased calcium

• however, keratinocytes differentiate normally in vivo

abnormal epidermis stratum corneum morphology ( J:122320 )

• free fatty acids and ceramide content are decreased in the outer layer of the epidermis

• lipid composition within the stratum corneum is altered resulting in defective epidermal barrier and increased transepidermal water loss

shiny skin ( J:122320 )

abnormal skin condition ( J:122320 )

• at birth skin is shiny, sticky and taut

cellular

abnormal keratinocyte differentiation ( J:122320 )

• primary keratinocytes do not differentiate in medium with increased calcium

• however, keratinocytes differentiate normally in vivo

Genotype
MGI:3804036

cn2

• Allelic Composition: Chuk^tm1Mpa/Chuk^tm1Mpa; Ikbkb^tm2Cgn/Ikbkb^tm2Cgn; Tg(Alb1-cre)7Gsc/0
• Genetic Background: involves: C57BL/6 * FVB/N

mortality/aging

decreased survivor rate ( J:137861 )

• most mice die by 7 months of age

premature death ( J:137861 )

• most mice die by 7 months of age

liver/biliary system

abnormal bile duct morphology ( J:137861 )

• the number of intact small portal bile ducts is reduced compared to in wild-type mice and exhibit signs of severe chronic cholestasis

• unobstructed bile ducts exhibit damaged, flattened epithelium surrounded by inflammatory foci with lymphocyte and ceroid macrophage infiltrate unlike in wild-type mice

• however, small bile duct development is normal at birth

• as the portal bile ducts are destroyed bile leaks between neighboring cells and the blood-bile barrier is disrupted

abnormal bile canaliculus morphology ( J:137861 )

• altered tubular arrangements of hepatocytes and severe dilations of the bile canaliculi are observed along with the disappearance of microvilli, formation of blebs and thickening of the pericanalicular ectoplasm

intrahepatic cholestasis ( J:137861 )

• severe chronic cholestasis in the liver

jaundice ( J:137861 )

homeostasis/metabolism

increased circulating bilirubin level ( J:137861 )

increased circulating alanine transaminase level ( J:137861 )

growth/size/body

cachexia ( J:137861 )

postnatal growth retardation ( J:137861 )

immune system

increased susceptibility to endotoxin shock ( J:137861 )

• following exposure to LPS, mice exhibit increased liver failure and hepatocyte apoptosis compared to similarly treated wild-type mice or single homozygous mice

endocrine/exocrine glands

abnormal bile duct morphology ( J:137861 )

• the number of intact small portal bile ducts is reduced compared to in wild-type mice and exhibit signs of severe chronic cholestasis

• unobstructed bile ducts exhibit damaged, flattened epithelium surrounded by inflammatory foci with lymphocyte and ceroid macrophage infiltrate unlike in wild-type mice

• however, small bile duct development is normal at birth

• as the portal bile ducts are destroyed bile leaks between neighboring cells and the blood-bile barrier is disrupted