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Abnormal bone marrow stroma in mice deficient for nemo-like kinase, Nlk.

TitleAbnormal bone marrow stroma in mice deficient for nemo-like kinase, Nlk.
Publication TypeJournal Article
Year of Publication2001
AuthorsKortenjann M, Nehls M, Smith AG, Carsetti R, Schüler J, Köhler G, Boehm T
JournalEur J Immunol
Volume31
Issue12
Pagination3580-7
Date Published2001 Dec
ISSN0014-2980
KeywordsAnimals, Bone Marrow Cells, Cell Differentiation, Hematopoiesis, Mice, Mice, Inbred C57BL, Mice, SCID, Mitogen-Activated Protein Kinases, Stromal Cells
Abstract

The stromal compartment of the bone marrow is composed of various cell types that provide trophic and instructive signals for hematopoiesis. The mesenchymal stem cell is believed to give rise to all major cellular components of the bone marrow microenvironment. Nemo-like kinase, Nlk, is a serine-threonine kinase that connects MAP kinase and Wnt signaling pathways; its in vivo function in mouse is unknown. We have generated mice with a targeted disruption of Nlk and find that the complex phenotype significantly varies with the genetic background. Whereas C57BL/6 mice lacking Nlk die during the third trimester of pregnancy, the 129/Sv background supports survival into adolescence; such mice are growth retarded and suffer from various neurological abnormalities. We show here that the Nlk deficiency syndrome includes aberrant differentiation of bone marrow stromal cells. Varying degrees of morphological abnormality, such as increased numbers of adipocytes, large blood sinuses and absence of bone-lining cells are observed in the bone marrow of mutant mice. Nlk deficient mice thus provide a novel model to study the genetic requirements for bone marrow stromal differentiation.

DOI10.1002/1521-4141(200112)31:12<3580::AID-IMMU3580>3.0.CO;2-N
Alternate JournalEur. J. Immunol.
PubMed ID11745377