Targeted Mutation of NGN3 Gene Disrupts Pancreatic Endocrine Cell Development in Pigs.

Scientific Reports
Timothy P SheetsBhanu P Telugu

Abstract

The domestic pig is an attractive model for biomedical research because of similarities in anatomy and physiology to humans. However, key gaps remain in our understanding of the role of developmental genes in pig, limiting its full potential. In this publication, the role of NEUROGENIN 3 (NGN3), a transcription factor involved in endocrine pancreas development has been investigated by CRISPR/Cas9 gene ablation. Precomplexed Cas9 ribonucleoproteins targeting NGN3 were injected into in vivo derived porcine embryos, and transferred into surrogate females. On day 60 of pregnancy, nine fetuses were collected for genotypic and phenotypic analysis. One of the piglets was identified as an in-frame biallelic knockout (Δ2/Δ2), which showed a loss of putative NGN3-downstream target genes: NEUROD1 and PAX4, as well as insulin, glucagon, somatostatin and pancreatic polypeptide-Y. Fibroblasts from this fetus were used in somatic cell nuclear transfer to generate clonal animals to qualify the effect of mutation on embryonic lethality. Three live piglets were born, received colostrum and suckled normally, but experienced extreme weight loss over a 24 to 36-hour period requiring humane euthanasia. Expression of pancreatic endocrine hormones: in...Continue Reading

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Citations

Nov 6, 2018·Annual Review of Animal Biosciences·Marko RudarTeresa A Davis
Feb 25, 2019·The Journal of Endocrinology·Jackson NteebaMichael Soares
May 30, 2019·In Vitro Cellular & Developmental Biology. Animal·Jing ZhangJinsheng Qi
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Dec 10, 2021·Biochemical Society Transactions·Mohamed SalehKrishna Prasadan

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Datasets Mentioned

BETA
KP796255

Methods Mentioned

BETA
genetic modifications
PCR
genotyping
biopsies
electrophoresis
restriction digest

Software Mentioned

OligodT
EMBOSS Stretcher
BLAST
BioEdit
CD
ClustalW
Search
Staden package

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