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克隆犬下颌骨发育不全可能与 Wnt 信号通路起始因子的变异有关。

Brachygnathia Inferior in Cloned Dogs Is Possibly Correlated with Variants of Wnt Signaling Pathway Initiators.

机构信息

Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea.

Animal Biotechnology Division, National Institute of Animal Science (NIAS), Rural Development Administration (RDA), 1500, Kongjwipatjwi-ro, Isero-myeon, Wanju 55365, Korea.

出版信息

Int J Mol Sci. 2022 Jan 1;23(1):475. doi: 10.3390/ijms23010475.

DOI:10.3390/ijms23010475
PMID:35008901
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8745273/
Abstract

Abnormalities in animals cloned via somatic cell nuclear transfer (SCNT) have been reported. In this study, to produce bomb-sniffing dogs, we successfully cloned four healthy dogs through SCNT using the same donor genome from the skin of a male German shepherd old dog. Veterinary diagnosis (X-ray/3D-CT imaging) revealed that two cloned dogs showed normal phenotypes, whereas the others showed abnormal shortening of the mandible (brachygnathia inferior) at 1 month after birth, even though they were cloned under the same conditions except for the oocyte source. Therefore, we aimed to determine the genetic cause of brachygnathia inferior in these cloned dogs. To determine the genetic defects related to brachygnathia inferior, we performed karyotyping and whole-genome sequencing (WGS) for identifying small genetic alterations in the genome, such as single-nucleotide variations or frameshifts. There were no chromosomal numerical abnormalities in all cloned dogs. However, WGS analysis revealed variants of Wnt signaling pathway initiators (WNT5B, DVL2, DACT1, ARRB2, FZD 4/8) and cadherin (CDH11, CDH1like) in cloned dogs with brachygnathia inferior. In conclusion, this study proposes that brachygnathia inferior in cloned dogs may be associated with variants in initiators and/or regulators of the Wnt/cadherin signaling pathway.

摘要

体细胞细胞核移植（SCNT）克隆动物的异常已被报道。在这项研究中，为了生产嗅探爆炸物的狗，我们成功地通过 SCNT 使用来自一只老年雄性德国牧羊犬皮肤的相同供体基因组克隆了四只健康的狗。兽医诊断（X 射线/3D-CT 成像）显示，两只克隆狗表现出正常的表型，而其他两只在出生后 1 个月表现出下颌骨异常缩短（下颌骨发育不全），尽管它们在除卵母细胞来源之外的相同条件下被克隆。因此，我们旨在确定这些克隆狗下颌骨发育不全的遗传原因。为了确定与下颌骨发育不全相关的遗传缺陷，我们进行了核型分析和全基因组测序（WGS），以鉴定基因组中的小遗传改变，如单核苷酸变异或移码。所有克隆狗均无染色体数目异常。然而，WGS 分析显示下颌骨发育不全的克隆狗中存在 Wnt 信号通路起始因子（WNT5B、DVL2、DACT1、ARRB2、FZD4/8）和钙粘蛋白（CDH11、CDH1-like）的变异。总之，本研究提出，克隆狗的下颌骨发育不全可能与 Wnt/cadherin 信号通路的起始因子和/或调节剂的变异有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc8/8745273/b089dd7b48f9/ijms-23-00475-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc8/8745273/83443420fc18/ijms-23-00475-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc8/8745273/3df9db983a47/ijms-23-00475-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc8/8745273/c78596dd968c/ijms-23-00475-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc8/8745273/6d0d0d33975b/ijms-23-00475-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc8/8745273/ceb4bd6f394b/ijms-23-00475-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc8/8745273/b089dd7b48f9/ijms-23-00475-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc8/8745273/83443420fc18/ijms-23-00475-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc8/8745273/3df9db983a47/ijms-23-00475-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc8/8745273/c78596dd968c/ijms-23-00475-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc8/8745273/6d0d0d33975b/ijms-23-00475-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc8/8745273/ceb4bd6f394b/ijms-23-00475-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc8/8745273/b089dd7b48f9/ijms-23-00475-g006.jpg

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