Research articleEctopic liver and gallbladder in a cloned dog: Possible nonheritable anomaly
Introduction
The term “choristoma” originally comes from the German word “to separate” and was introduced by Eugen Albrecht in 1904 to refer to a mass of normal tissue located at a site away from its usual location [1]. Choristoma occurring with hepatic or gallbladder tissue is commonly called ectopic or heterotopic liver or gallbladder. Ectopic liver and gallbladder have been recorded since the 19th century [2], but only less than 80 cases of ectopic liver were documented in a recent literature review [3] with lower than 0.5% [4] and 0.4% [5] incidences. Ectopic liver has been found in various sites including the gallbladder [3], [6], [7], spleen [8], pancreas [9], stomach [10], heart [11], lung [12] and suprahepatic inferior vena cava [13], [14], and ectopic gallbladder has been described in the intrahepatic [15] and suprahepatic region [16], and left hepatic lobe [17], [18]. Both anomalies are usually asymptomatic, but rare symptoms such as intra-abdominal bleeding due to ectopic liver [10] or epigastric pain caused by ectopic gallbladder [17] have been reported. Lack of symptoms usually results in discovery of these anomalies only during peritoneoscopy, laparotomy, or autopsy. Also, almost all the documented cases of these anomalies have been described in human beings, not in animals [1], [2], [3], [4], [5], [6], [8], [9], [10], [11], [12], [15], [16], [17], [18], [19], [20], [21]. In dogs, ectopic hepatocytes were firstly reported in 2005, in which a bearded collie had a firm and nonpainful mass in the left midabdominal region [22]. Consequently, scarcity of the anomaly, lack of symptoms, and absence of animal models have made it hard to define a cause of ectopic liver and gallbladder.
Somatic cell nuclear transfer (SCNT) is a process for producing genetically identical organisms asexually [23] which includes nuclear removal from a donor oocyte, donor cell injection into the empty perivitelline space, fusion between the cytoplast–cell couplet, and activation of the reconstructed embryo. Since the first cloned animal, Dolly the sheep, was produced using SCNT in 1997 [24], more than 16 mammalian species including mice [25], rats [26], cattle [27], pigs [28], cats [29], and dogs [30] have been successfully produced. Among these, dogs have advantages as animal models for human diseases because of the similarities in their size, longevity, and physiology to humans. Of the nearly 648 known hereditary diseases described in dogs, more than half (352) can be potential models for human diseases (http://omia.angis.org.au, January 2014). A human disease model dog can be generated by replacing a donor oocyte's nucleus with a cell derived from a dog naturally having a heritable disease or with a cell containing a genetically modified transgene [31], [32]. For example, a cloned puppy derived from a donor dog having hip dysplasia, which is an inherited disease characterized by hip subluxation and laxity [33], [34], also showed signs of hip dysplasia. Because of the identical genetic traits between donor and cloned dogs, SCNT can be used as a tool for studying potential causes of unidentified disease to determine whether it is caused by a genetic modification or not.
In the present study, we report for the first time an occurrence of both ectopic liver and gallbladder in a cloned dog and aimed to investigate their etiology by recloning using cells derived from the clone.
Section snippets
Animal use
Animal experiments were done following a standard procedure established by the Committee for Accreditation of Laboratory Animal Care and the Guideline for the Care and Use of Laboratory Animals of Seoul National University (approval number is SNU-121130-1).
Production of a cloned dog
Ear skin tissue from a 10-year-old male beagle (Fig. 1A) was collected and transferred to the laboratory aseptically. The tissue was minced and cultured with Dulbecco's modified Eagle's medium (Invitrogen, Carlsbad, CA, USA) supplemented with
Gross pathologic examination of ectopic organs found in a cloned dog
A cloned dog died on the day of birth because of cannibalism by its nanny dog. During the routine autopsy, ectopic organs assumed to be liver and gallbladder were found between the left-side ribs and the skin (Fig. 2A). Although there was a properly located liver (mother liver) with six lobes, no gallbladder was present in the abdominal cavity. Interestingly, there was a well-defined, large solid mass (6 × 4 × 0.5 cm) with a smooth surface and reddish brown color similar to the normal liver
Discussion
Ectopic organs are rare congenital abnormalities. Several organs including the liver [1], [2], [3], [4], [5], [6], [8], [9], [10], [11], [12], [15], [16], [17], [18], [19], gallbladder [5], [17], [19], pancreas [39], kidney [40], testis [41], and ovary [42] located in ectopic positions have been reported in humans. Because the aberrant tissue is often not accompanied by any clinical relevance [3], [19], [39], it has a low incidence rate and it is difficult to analyze the reason for its
Acknowledgments
This study was supported by Rural Development Administration (#PJ010928032015), Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (#311062-04-3SB010), National Research Foundation of Korea (#2014R1A1A2059928), Research Institute for Veterinary Science, Natural Balance Korea, and the BK21 plus program. The authors thank Dr Barry D. Bavister for his valuable editing of the article.
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