Phenotypes associated with this allele

• Allele Symbol: Sox17^tm1Ysk
• Allele Name: targeted mutation 1, Yoshiakira Kanai
• Allele ID: MGI:2179440
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Sox17^tm1Ysk/Sox17^tm1Ysk	involves: 129S1/Sv	MGI:2180006
ht2	Sox17^tm1Ysk/Sox17^+	B6.129S1-Sox17^tm1Ysk	MGI:6113926
ht3	Sox17^tm1Ysk/Sox17^+	involves: 129S1/Sv * C57BL/6	MGI:6113921
cx4	Shh^tm1(EGFP/cre)Cjt/Shh^+ Sox17^tm1Ysk/Sox17^+	involves: 129S1/Sv * C57BL/6	MGI:6113949

Genotype
MGI:2180006

hm1

• Allelic Composition: Sox17^tm1Ysk/Sox17^tm1Ysk
• Genetic Background: involves: 129S1/Sv

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:75946 )

• embryos die at E10.5

digestive/alimentary system

abnormal foregut morphology ( J:75946 )

• at E9.5, the foregut was small in size and deficient of endodermal cells; definitive gut endoderm was absent from the lateral region of the embryonic gut

abnormal hindgut morphology ( J:75946 )

• at E9.5, the hindgut has regressed to a cord-like structure containing significantly fewer endodermal cells

abnormal midgut morphology ( J:75946 )

• at E9.5, the midgut has degenerated into a cord-like structure

embryo

failure of initiation of embryo turning ( J:75946 )

• embryos did not exhibit axis rotation

abnormal endoderm development ( J:75946 )

• at E8.25, cells in the lateral region exhibited an abnormal morphology consistent with visceral endoderm

• the endodermal layer was not separated from the mesothelium by a layer of splanchnic mesenchyme

abnormal rostral-caudal axis patterning ( J:75946 )

• growth and morphogenesis of the posterior trunk was disorganized after E9.5

thin endoderm ( J:75946 )

• at E8.0, the definitive endoderm was reduced at the posterior and lateral regions

Genotype
MGI:6113926

ht2

• Allelic Composition: Sox17^tm1Ysk/Sox17⁺
• Genetic Background: B6.129S1-Sox17^tm1Ysk

muscle

abnormal gallbladder smooth muscle morphology ( J:241569 )

• formation of smooth muscle layers in gallbladders is delayed and defective with smooth muscle cells distributed randomly and irregularly with a swirling pattern distinct from wild-type mice at E17

• E13.5 gallbladder explants grown in an in vitro culture system show poor development of the smooth muscle layer

mortality/aging

perinatal lethality, incomplete penetrance ( J:194071 )

• perinatal lethality in about 90% of pups after the N5 generation of the backcross onto C57BL/6

neonatal lethality, incomplete penetrance ( J:241569 )

• mice maintained at F8-9 backcross to C57BL/6 show approximate 70% neonatal lethality; remaining mice survive to adulthood

liver/biliary system

abnormal bile duct development ( J:194071 )

• defects in development of the bile duct systems during late-organogenic stages

abnormal extrahepatic bile duct morphology ( J:194071 )

• 21 of 22 fetuses show ectopic extrahepatic ducts in the cystic duct region

biliary atresia ( J:241569 )

abnormal gallbladder morphology ( J:194071 , J:241569 )

• defects in development of the gallbladder during late-organogenic stages (J:194071)

• gallbladder hypoplasia is seen in almost all fetuses and is seen as early as E15.5 (J:194071)

• however, lung, pancreas, esophagus, stomach, duodenum and intestine appear normal (J:194071)

• severe hypotrophy of the gallbladder (J:241569)

• E13.5 gallbladder explants grown in an in vitro culture system show poor development with only a single-layered cuboidal epithelium without any epithelial fold formation and poor development of the smooth muscle layer (J:241569)

• gallbladder explants incubated with SHH-soaked beads show rescue of the gallbladder developmental defects (J:241569)

abnormal gallbladder epithelium morphology ( J:194071 , J:241569 )

• hypoplasia of the gallbladder epithelium as early as E15.5-16.5 (J:194071)

• gallbladder forms a hypotrophic, single-layered cuboidal epithelium with no epithelial fold formation by E17.5 and reduced height compared to a pseudostratified columnar epithelium in wild-type mice (J:194071)

• PCNA-positive indices and Ki-67 and BrdU-labeling indices in the gallbladder epithelia are reduced at E15.5 (J:194071)

• epithelial cell deciduation in the gallbladder (J:194071)

• frequencies of primary cilia in the gallbladder epithelia are increased (J:194071)

• organ culture of gallbladder primordia shows defective elongation and shredding of epithelial cells in bile duct epithelia (J:194071)

• gallbladder epithelium exhibits cystic duct-like phenotypes (J:241569)

small gallbladder ( J:241569 )

• in surviving adults

abnormal gallbladder smooth muscle morphology ( J:241569 )

• formation of smooth muscle layers in gallbladders is delayed and defective with smooth muscle cells distributed randomly and irregularly with a swirling pattern distinct from wild-type mice at E17

• E13.5 gallbladder explants grown in an in vitro culture system show poor development of the smooth muscle layer

liver inflammation ( J:194071 )

• marker analysis indicates perinatal onset of hepatic inflammation in livers during E16.5-E17.5 indicating acute hepatitis in fetuses

• Background Sensitivity: hepatitis is more severe on the C57BL/6 background than on a mixed background

abnormal liver development ( J:194071 )

• defects in development of liver during late-organogenic stages

abnormal liver lobule morphology ( J:194071 )

• 62.5% of fetuses backcrossed to C57BL/6 for 7-8 generations show peripheral degeneration of liver lobules with varying severity at E17.5

• peripheral degeneration of liver lobules is first seen at E16.5-E17 and degeneration rapidly expands toward the central proximal region of the lobules

abnormal hepatocyte morphology ( J:194071 )

• endoplasmic reticulum enlargement in the cytoplasmic region facing the bile canaliculi in the hepatocytes around the degenerative region

decreased liver weight ( J:194071 )

• liver weight is reduced at E16.5

cholestasis ( J:194071 , J:241569 )

• development of cholestasis at E16.5-17.5 (J:194071)

extrahepatic cholestasis ( J:194071 )

• gallbladder epithelial cells are occasionally detached from the gallbladder wall and accumulate inside the lumina of the cystic and extrahepatic duct where these cells cause stenosis and atresia in the cystic and extrahepatic ducts to varying degrees

abnormal gallbladder physiology ( J:241569 )

• KCl treatment causes no contraction of the fetal gallbladder at E17.5 in mildly and severely affected mutants, while in the severely affected mice, KCl-induced contraction is reduced

• -autonomous gallbladder contraction is reduced at E17.5

gallbladder inflammation ( J:241569 )

• marker analysis indicates onset of cholecytitis in gallbladder during fetal stages

endocrine/exocrine glands

abnormal bile duct development ( J:194071 )

• defects in development of the bile duct systems during late-organogenic stages

abnormal extrahepatic bile duct morphology ( J:194071 )

• 21 of 22 fetuses show ectopic extrahepatic ducts in the cystic duct region

biliary atresia ( J:241569 )

abnormal gallbladder morphology ( J:194071 , J:241569 )

• defects in development of the gallbladder during late-organogenic stages (J:194071)

• gallbladder hypoplasia is seen in almost all fetuses and is seen as early as E15.5 (J:194071)

• however, lung, pancreas, esophagus, stomach, duodenum and intestine appear normal (J:194071)

• severe hypotrophy of the gallbladder (J:241569)

• E13.5 gallbladder explants grown in an in vitro culture system show poor development with only a single-layered cuboidal epithelium without any epithelial fold formation and poor development of the smooth muscle layer (J:241569)

• gallbladder explants incubated with SHH-soaked beads show rescue of the gallbladder developmental defects (J:241569)

abnormal gallbladder epithelium morphology ( J:194071 , J:241569 )

• hypoplasia of the gallbladder epithelium as early as E15.5-16.5 (J:194071)

• gallbladder forms a hypotrophic, single-layered cuboidal epithelium with no epithelial fold formation by E17.5 and reduced height compared to a pseudostratified columnar epithelium in wild-type mice (J:194071)

• PCNA-positive indices and Ki-67 and BrdU-labeling indices in the gallbladder epithelia are reduced at E15.5 (J:194071)

• epithelial cell deciduation in the gallbladder (J:194071)

• frequencies of primary cilia in the gallbladder epithelia are increased (J:194071)

• organ culture of gallbladder primordia shows defective elongation and shredding of epithelial cells in bile duct epithelia (J:194071)

• gallbladder epithelium exhibits cystic duct-like phenotypes (J:241569)

small gallbladder ( J:241569 )

• in surviving adults

abnormal gallbladder smooth muscle morphology ( J:241569 )

• formation of smooth muscle layers in gallbladders is delayed and defective with smooth muscle cells distributed randomly and irregularly with a swirling pattern distinct from wild-type mice at E17

• E13.5 gallbladder explants grown in an in vitro culture system show poor development of the smooth muscle layer

homeostasis/metabolism

increased circulating alanine transaminase level ( J:194071 )

• levels of serum ALT are elevated at E17

increased circulating alkaline phosphatase level ( J:194071 )

• serum levels of ALP are elevated at E17

increased bile salt level ( J:194071 )

• intrahepatic levels of bile acids is elevated in livers at E17

immune system

gallbladder inflammation ( J:241569 )

• marker analysis indicates onset of cholecytitis in gallbladder during fetal stages

liver inflammation ( J:194071 )

• marker analysis indicates perinatal onset of hepatic inflammation in livers during E16.5-E17.5 indicating acute hepatitis in fetuses

• Background Sensitivity: hepatitis is more severe on the C57BL/6 background than on a mixed background

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
biliary atresia		DOID:13608	OMIM:210500	J:194071 , J:241569

Genotype
MGI:6113921

ht3

• Allelic Composition: Sox17^tm1Ysk/Sox17⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

endocrine/exocrine glands

abnormal extrahepatic bile duct morphology ( J:194071 )

• Background Sensitivity: ectopic hepatic duct phenotypes are milder on the mixed background compared to on a C57BL/6 background

abnormal gallbladder morphology ( J:194071 )

• gallbladder hypoplasia is seen in almost all adults

immune system

liver inflammation ( J:194071 )

• Background Sensitivity: hepatitis phenotypes are milder on the mixed background compared to on a C57BL/6 background

liver/biliary system

abnormal extrahepatic bile duct morphology ( J:194071 )

• Background Sensitivity: ectopic hepatic duct phenotypes are milder on the mixed background compared to on a C57BL/6 background

abnormal gallbladder morphology ( J:194071 )

• gallbladder hypoplasia is seen in almost all adults

liver inflammation ( J:194071 )

• Background Sensitivity: hepatitis phenotypes are milder on the mixed background compared to on a C57BL/6 background

Genotype
MGI:6113949

cx4

• Allelic Composition: Shh^{tm1(EGFP/cre)Cjt}/Shh⁺; Sox17^tm1Ysk/Sox17⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

endocrine/exocrine glands

abnormal gallbladder smooth muscle morphology ( J:241569 )

• formation of smooth muscle layers in gallbladders is more severely delayed and defective than in either single mutant

muscle

abnormal gallbladder smooth muscle morphology ( J:241569 )

• formation of smooth muscle layers in gallbladders is more severely delayed and defective than in either single mutant

liver/biliary system

abnormal gallbladder smooth muscle morphology ( J:241569 )

• formation of smooth muscle layers in gallbladders is more severely delayed and defective than in either single mutant