Phenotypes associated with this allele

• Allele Symbol: Krt8^tm1Rgo
• Allele Name: targeted mutation 1, Robert G Oshima
• Allele ID: MGI:2178042
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Krt8^tm1Rgo/Krt8^tm1Rgo	involves: 129S2/SvPas * C57BL/6	MGI:2178044
hm2	Krt8^tm1Rgo/Krt8^tm1Rgo	involves: 129S2/SvPas * C57BL/6 * FVB/N	MGI:3582871
cx3	Krt19^tm2Mmt/Krt19^tm2Mmt Krt8^tm1Rgo/Krt8^tm1Rgo	FVB.129S2-Krt19^tm2Mmt Krt8^tm1Rgo	MGI:3850373
cx4	Krt8^tm1Rgo/Krt8^tm1Rgo Tnfrsf1b^tm1Mwm/Tnfrsf1b^tm1Mwm	involves: 129S2/SvPas * C57BL/6 * FVB/N	MGI:3711995
cx5	Krt8^tm1Rgo/Krt8^tm1Rgo Tnf^tm1Gkl/Tnf^tm1Gkl	involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * FVB/N	MGI:3711994

Genotype
MGI:2178044

hm1

• Allelic Composition: Krt8^tm1Rgo/Krt8^tm1Rgo
• Genetic Background: involves: 129S2/SvPas * C57BL/6

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

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:12899 , J:121811 )

• normal survival through E9.5 (J:12899)

• dramatically reduced survival between E12 and E13 (J:12899)

• Background Sensitivity: small proportion of homozygotes (6%) survive to adulthood on this background (J:12899)

• tetraploid rescue of embryonic lethality (J:121811)

embryo

decreased embryo weight ( J:12899 )

• 65-70% of normal weight by E12.5

abnormal placenta morphology ( J:121811 )

• partially coagulated blood accumulates between the decidua and the yolk sac

abnormal trophoblast layer morphology ( J:121811 )

• disruption of the trophoblast giant cell layer

abnormal trophoblast giant cell morphology ( J:121811 )

• degeneration of trophoblast giant cells

abnormal extraembryonic tissue physiology ( J:121811 )

• massive hemorrhage of maternal blood between the deciduas capsularis and the parietal yolk sac

impaired placental function ( J:121811 )

cardiovascular system

internal hemorrhage ( J:12899 )

• internal bleeding observed in some embryos

hematopoietic system

extramedullary hematopoiesis ( J:12899 )

• abnormal accumulations of nucleated embryonic erythrocytes in the liver at E12.5

reproductive system

reduced female fertility ( J:12899 )

♀ • Background Sensitivity: reduced female fertility

growth/size/body

decreased embryo weight ( J:12899 )

• 65-70% of normal weight by E12.5

Genotype
MGI:3582871

hm2

• Allelic Composition: Krt8^tm1Rgo/Krt8^tm1Rgo
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * FVB/N

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:22116 )

• Background Sensitivity: 36% of homozygotes survive to adulthood after one backcross to FVB/N

• Background Sensitivity: 55% of homozygotes survive to adulthood after two or more backcrosses to FVB/N

digestive/alimentary system

abnormal intestinal epithelium morphology ( J:118021 )

• mistargeting of apical membrane proteins in the epithelium of the small intestine

abnormal colon morphology ( J:22116 , J:89299 )

• hyperplastic lesions in the colon and rectum (J:22116)

• elongated villi (J:22116)

• frequent mitotic colonocytes (J:89299)

• colonocyte sloughing into the lumen in some areas (J:89299)

rectal prolapse ( J:22116 )

• anorectal prolapse developing between 9 weeks and 1 year of age

diarrhea ( J:89299 )

• watery stools

abnormal intestinal mineral absorption ( J:89299 )

• decreased net sodium absorption

• significantly decreased net chloride flux resulting in net chloride secretion

hematopoietic system

enlarged spleen ( J:22116 )

• moderate splenomegaly

liver/biliary system

liver hemorrhage ( J:86719 )

• increased hemorrhage seen in the liver on a lithogenic diet

hepatic necrosis ( J:22116 , J:86719 )

abnormal hepatocyte morphology ( J:44938 , J:86719 , J:106541 , J:121813 )

• reduced viability of hepatocytes isolated by collagenase perfusion compared to wild-type (J:44938)

• nucleus of hepatocytes often displaced to the periphery of the cell when on a lithogenic diet (J:86719)

• liver lesions, necrosis and abnormal hepatocyte cell cycle correlating with multinuclear cells and abnormal hepatocellular architecture (J:106541)

• increased sensitivity of hepatocytes to apoptosis (J:121814) (J:121813)

hepatic steatosis ( J:86719 )

• liver steatosis develops on a lithogenic diet

cardiovascular system

liver hemorrhage ( J:86719 )

• increased hemorrhage seen in the liver on a lithogenic diet

immune system

enlarged spleen ( J:22116 )

• moderate splenomegaly

chronic inflammation ( J:86719 , J:98058 )

• increased inflammation on a lithogenic diet (J:86719)

• Th-2 mediated inflammation of the colon (J:98058)

reproductive system

female infertility ( J:22116 )

♀ • Background Sensitivity: females are sterile but males are normally fertile

growth/size/body

decreased body weight ( J:89299 )

enlarged spleen ( J:22116 )

• moderate splenomegaly

cellular

hepatic necrosis ( J:22116 , J:86719 )

Genotype
MGI:3850373

cx3

• Allelic Composition: Krt19^tm2Mmt/Krt19^tm2Mmt; Krt8^tm1Rgo/Krt8^tm1Rgo
• Genetic Background: FVB.129S2-Krt19^tm2Mmt Krt8^tm1Rgo

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:65498 )

• after E9.5, the number of double homozygotes declines gradually, with increasing numbers of necrotic remnants and resorption sites

• although some double homozygotes are still alive at E9.75-E10.5, they exhibit small placentas and varying degrees of growth retardation

embryo

embryonic growth retardation ( J:65498 )

• at E9.75-E10.5, live double homozygotes display varying degrees of growth retardation

abnormal allantois morphology ( J:65498 )

• at E10.5, the allantois is poorly formed and shows signs of degeneration

abnormal placenta morphology ( J:65498 )

• as early as E9.5, double homozygotes display placental defects that cause flooding of the maternal blood into the embryonic placenta

abnormal placenta labyrinth morphology ( J:65498 )

• at E9.5, labyrinthine trophoblast cells are decreased in number and appear to be poorly organized

• at E10.5, degeneration of the labyrinthine trophoblasts is observed

abnormal placental labyrinth vasculature morphology ( J:65498 )

• by E10.5, placental vascular structures are deteriorated while maternal and embryonic blood cells display signs of degeneration

small placenta ( J:65498 )

• at E9.75-E10.5, placentas are smaller than normal

abnormal trophoblast layer morphology ( J:65498 )

• at E10.5, trophoblastic tissues contain lesions filled with unnucleated maternal erythrocytes as well as some large and nucleated embryonic erythrocytes

abnormal trophoblast giant cell morphology ( J:65498 )

• at E9.5, giant trophoblasts are pulled apart and display significantly larger cell bodies and nuclei

increased trophoblast giant cell number ( J:65498 )

• a significant increase in the number of secondary giant cells is noted at E9.5

• at E10.5, multiple layers of giant cells are observed

abnormal spongiotrophoblast layer morphology ( J:65498 )

• at E10.5, degeneration of the spongiotrophoblasts is observed

abnormal spongiotrophoblast cell morphology ( J:65498 )

• at E9.5, spongiotrophoblast cells appear to be poorly organized

decreased spongiotrophoblast cell number ( J:65498 )

• at E9.5, spongiotrophoblast cells are decreased in number

impaired placental function ( J:65498 )

• at E9.5, double homozygotes display flooding of maternal blood into the embryonic placenta in the absence of overt clotting

growth/size/body

embryonic growth retardation ( J:65498 )

• at E9.75-E10.5, live double homozygotes display varying degrees of growth retardation

cardiovascular system

abnormal placental labyrinth vasculature morphology ( J:65498 )

• by E10.5, placental vascular structures are deteriorated while maternal and embryonic blood cells display signs of degeneration

Genotype
MGI:3711995

cx4

• Allelic Composition: Krt8^tm1Rgo/Krt8^tm1Rgo; Tnfrsf1b^tm1Mwm/Tnfrsf1b^tm1Mwm
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * FVB/N

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:121811 )

• survival improved 4 fold in the absence of maternal TNFRSF1b as compared to the condition in which TNFRSF1b was present

• survival continues to be reduced

Genotype
MGI:3711994

cx5

• Allelic Composition: Krt8^tm1Rgo/Krt8^tm1Rgo; Tnf^tm1Gkl/Tnf^tm1Gkl
• Genetic Background: involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * FVB/N

mortality/aging

mortality/aging ( J:121811 )

N • about 60% survive beyond 250 days

prenatal lethality, incomplete penetrance ( J:121811 )

• Background Sensitivity: about 50% survive to birth as opposed to 25% when maternal TNF is produced