NDLI: Knock-in of diphteria toxin A chain gene at Ins2 locus: effects on islet development and localization of Ins2 expression in the brain

Content Provider	Springer Nature Link
Author	Lamotte, Luciane Jackerott, Malene Bucchini, Danielle Jami, Jacques Joshi, Rajiv Deltour, Louise
Copyright Year	2004
Abstract	We report here knock-in of diphteria toxin A chain (dta) gene at the Ins2 locus, using the strategy previously employed to insert lacZ under control of the Ins2 promoter. Mutant Ins2$^{ dta/+}$, Ins2$^{ dta/lacZ }$ or Ins2$^{ lacZ/+}$ mouse pups were generated by breeding and analyzed to study the effects of toxigenetic β-cell ablation on islet development and to localize the extrapancreatic Ins2 expression site in the brain. Ins2$^{ dta/+}$ and Ins2$^{ dta/lacZ }$ pups developed a severe diabetic ketoacidosis and died rapidly. Histological analysis of their pancreas revealed that β-cells completely disappeared in their islets as evidenced by loss of lacZ activity or insulin immunonostaining. β-cell ablation did not alter the size of other islet cell populations which were normal at birth, although the glucagon-cell population was reduced by 85% at embryonic day E12.5. In the brain, comparative analysis of lacZ expression in Ins2$^{ lacZ/+}$ and Ins2$^{ dta/lacZ }$ mice identified the choroid plexus (CP) as a major Ins2 expression site. This finding was confirmed by RT-PCR analysis of insulin transcripts in RNAs prepared from microdissected wild-type CP. Transcripts for other key β-cell markers, with the notable exception of Pdx-1, were also found in CP RNAs. These results must revive interest in studies focused on extrapancreatic insulin gene expression.
Starting Page	463
Ending Page	473
Page Count	11
File Format	PDF
ISSN	09628819
Journal	Transgenic Research
Volume Number	13
Issue Number	5
e-ISSN	15739368
Language	English
Publisher	Kluwer Academic Publishers
Publisher Date	2004-01-01
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Human Genetics Plant Sciences Animal Anatomy / Morphology / Histology
Content Type	Text
Resource Type	Article
Subject	Genetics Animal Science and Zoology Biotechnology Agronomy and Crop Science

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