TY - JOUR
T1 - Generation of heterozygous PKD1 mutant pigs exhibiting early-onset renal cyst formation
AU - Watanabe, Masahito
AU - Umeyama, Kazuhiro
AU - Nakano, Kazuaki
AU - Matsunari, Hitomi
AU - Fukuda, Toru
AU - Matsumoto, Kei
AU - Tajiri, Susumu
AU - Yamanaka, Shuichiro
AU - Hasegawa, Koki
AU - Okamoto, Kazutoshi
AU - Uchikura, Ayuko
AU - Takayanagi, Shuko
AU - Nagaya, Masaki
AU - Yokoo, Takashi
AU - Nakauchi, Hiromitsu
AU - Nagashima, Hiroshi
N1 - Funding Information:
This work was supported by Grants-in-Aid form the Meiji University International Institute for Bio-Resource Research (MUIIBR) and the Japan Agency for Medical Research and Development (AMED-LEAP, Generation of Functional Organs using developmental niches, JP19gm0010002).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/5
Y1 - 2022/5
N2 - Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, manifesting as the progressive development of fluid-filled renal cysts. In approximately half of all patients with ADPKD, end-stage renal disease results in decreased renal function. In this study, we used CRISPR-Cas9 and somatic cell cloning to produce pigs with the unique mutation c.152_153insG (PKD1insG/+). Pathological analysis of founder cloned animals and progeny revealed that PKD1insG/+ pigs developed many pathological conditions similar to those of patients with heterozygous mutations in PKD1. Pathological similarities included the formation of macroscopic renal cysts at the neonatal stage, number and cystogenic dynamics of the renal cysts formed, interstitial fibrosis of the renal tissue, and presence of a premature asymptomatic stage. Our findings demonstrate that PKD1insG/+ pigs recapitulate the characteristic symptoms of ADPKD.
AB - Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, manifesting as the progressive development of fluid-filled renal cysts. In approximately half of all patients with ADPKD, end-stage renal disease results in decreased renal function. In this study, we used CRISPR-Cas9 and somatic cell cloning to produce pigs with the unique mutation c.152_153insG (PKD1insG/+). Pathological analysis of founder cloned animals and progeny revealed that PKD1insG/+ pigs developed many pathological conditions similar to those of patients with heterozygous mutations in PKD1. Pathological similarities included the formation of macroscopic renal cysts at the neonatal stage, number and cystogenic dynamics of the renal cysts formed, interstitial fibrosis of the renal tissue, and presence of a premature asymptomatic stage. Our findings demonstrate that PKD1insG/+ pigs recapitulate the characteristic symptoms of ADPKD.
UR - http://www.scopus.com/inward/record.url?scp=85122177488&partnerID=8YFLogxK
U2 - 10.1038/s41374-021-00717-z
DO - 10.1038/s41374-021-00717-z
M3 - Article
AN - SCOPUS:85122177488
VL - 102
SP - 560
EP - 569
JO - Laboratory Investigation
JF - Laboratory Investigation
SN - 0023-6837
IS - 5
ER -