Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 45, Pages 18324-18329Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1112064108
Keywords
natural killer cell differentiation; NKp46 knock-in
Categories
Funding
- European Research Council
- Agence Nationale de la Recherche (ANR)
- Ligue Nationale Contre le Cancer (Equipe Labellisee La Ligue)
- Institut National de la Sante et de la Recherche Medicale
- Centre National de la Recherche Scientifique
- Universite de la Mediterranee
- ANR [R08063AS]
- Region Provence Alpes Cote d'Azur
- Innate-Pharma
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NKp46 is a cell surface receptor expressed on natural killer (NK) cells, on a minute subset of T cells, and on a population of innate lymphoid cells that produce IL-22 and express the transcription factor retinoid-related orphan receptor (ROR)-gamma t, referred to as NK cell receptor (NKR)(+)ROR-gamma t(+) cells. Here we describe Nkp46(iCre) knock-in mice in which the gene encoding the improved Cre (iCre) recombinase was inserted into the Nkp46 locus. This mouse was used to noninvasively trace cells expressing NKp46 in vivo. Fate mapping experiments demonstrated the stable expression of NKp46 on NK cells and allowed a reappraisal of the sequential steps of NK cell maturation. NKp46 genetic tracing also showed that gut NKR(+)ROR-gamma t(+) and NK cells represent two distinct lineages. In addition, the genetic heterogeneity of liver NK cells was evidenced. Finally, Nkp46(iCre) mice also represent a unique mouse model of conditional mutagenesis specifically in NKp46(+) cells, paving the way for further developments in the biology of NKp46(+) NK, T, and NKR(+)ROR-gamma t(+) cells.
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