Anatomical and histological characteristics of the hepatobiliary system in adult Sox17 heterozygote mice
Anatomical and histological characteristics of the hepatobiliary system in adult Sox17 heterozygote mice
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成年Sox17杂合子小鼠肝胆系统的解剖和组织学特征
作者：
Pattarapanawan M;Uemura M;Miyazaki N;Takami S;Tomiyasu H;Tsunekawa N;Hirate Y;Fujishiro J;Kurohmaru M;Kanai-Azuma M;Higashiyama H;Kanai Y.
摘要胆道闭锁是一种罕见的新生儿疾病，其主要表现为肝外胆管发炎及阻塞。Sox 17-haploinsufficient（Sox 17 +/−）小鼠是一种BA动物模型，包括胆管损伤和随后的新生期BA样炎症。大多数Sox 17 +/−的新生儿出生后很快死亡，但一些Sox 17 +/−的幼崽达到成年并有正常的寿命，不像人类BA。然而，存活Sox 17 +/−小鼠肝胆器官中的表型和BA源性瘢痕尚不清楚。在这里，我们检查了断奶后和年轻成年Sox 17 +/−小鼠的肝胆器官表型。结果证实，与野生型（WT）同窝小鼠相比，存活Sox 17 +/−小鼠的肝脏重量显著降低，同时伴有外周钙质沉着和肝小叶血管异常。这种肝脏表型可能是胎儿和新生儿阶段肝胆损伤的后遗症，这一观点得到了成年Sox 17 +/−小鼠肝损伤血清标志物水平轻微但显著增加的支持。存活的Sox 17 +/−小鼠胆囊较短，其中异位肝管比WT小鼠更常见。此外，存活的Sox 17 +/−小鼠既没有表现出EHBDs的阻塞，也没有表现出肝细胞或肝内导管的萎缩或炎症。这些数据表明，一些患有BA的Sox 17 +/−幼仔在围产期自然逃脱致死性并从胎儿肝胆损伤中恢复，突出了体内模型在理解人BA手术恢复胆汁流后肝胆愈合过程中的有用性。
Biliary atresia (BA) is a rare neonatal disease characterized by inflammation and obstruction of the extrahepatic bile ducts (EHBDs). TheSox17‐haploinsufficient (Sox17+/−) mouse is an animal model of BA that encompasses bile duct injury and subsequent BA‐like inflammation by the neonatal stage. MostSox17+/−neonates die soon after birth, but someSox17+/−pups reach adulthood and have a normal life span, unlike human BA. However, the phenotype and BA‐derived scars in the hepatobiliary organs of survivingSox17+/−mice are unknown. Here, we examined the phenotypes of the hepatobiliary organs in post‐weaning and young adultSox17+/−mice. The results confirmed the significant reduction in liver weight, together with peripheral calcinosis and aberrant vasculature in the hepatic lobule, in survivingSox17+/−mice as compared with their wild‐type (WT) littermates. Such hepatic phenotypes may be sequelae of hepatobiliary damage at the fetal and neonatal stages, a notion supported by the slight, but significant, increases in the levels of serum markers of liver damage in adultSox17+/−mice. The survivingSox17+/−mice had a shorter gallbladder in which ectopic hepatic ducts were more frequent compared to WT mice. Also, the survivingSox17+/−mice showed neither obstruction of the EHBDs nor atrophy or inflammation of hepatocytes or the intrahepatic ducts. These data suggest that someSox17+/−pups with BA naturally escape lethality and recover from fetal hepatobiliary damages during the perinatal period, highlighting the usefulness of the in vivo model in understanding the hepatobiliary healing processes after surgical restoration of bile flow in human BA.
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影响因子：
4.3
作者：
T. Murakami;D. Morioka;Hideki Takakura;Y. Miura;S. Togo
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S. Togo
影响因子：
2.4
作者：
Garcia AV;Cowles RA;Kato T;Hardy MA
通讯作者：
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影响因子：
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作者：
Spence, Jason R.;Lange, Alex W.;Lin, Suh-Chin J.;Kaestner, Klaus H.;Lowy, Andrew M.;Kim, Injune;Whitsett, Jeffrey A.;Wells, James M.
通讯作者：
Wells, James M.
DOI：
10.1097/mpg.0000000000002446
发表时间：
2019-10-01
影响因子：
2.9
作者：
Fanna, Martina;Masson, Guillaume;Chardot, Christophe
通讯作者：
Chardot, Christophe
未矫正的胆道闭锁的预后：更新。
影响因子：
2.4
作者：
S. Adelman
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S. Adelman