title: Normal growth and development in mice over-expressing the CCN family member WISP3.
abstract: Loss-of-function mutations in the gene WISP3 cause the autosomal recessive human skeletal disease Progressive Pseudorheumatoid Dysplasia, whereas mice with knockout mutations of Wisp3 have no phenotype. The lack of a phenotype in the Wisp3 knockout mice has constrained studies of the protein's in vivo function. Over-expression experiments in zebrafish indicated that WISP3 may function as a BMP and Wnt signaling modulator. To determine whether these biologic activities are retained in mice, we created two strains of transgenic mice that over-express WISP3 in a broad array of tissues. Despite strong and persistent protein over-expression, the transgenic mice remained phenotypically indistinguishable from their non-transgenic littermates. Surprisingly, WISP3 contained in conditioned medium recovered from transgenic mouse primary kidney cell cultures was able to bind BMP and to inhibit BMP signaling in vitro. Factors that account for the difference between the in vitro and in vivo activities of WISP3 remain unknown. At present, the mouse remains a challenging model organism in which to explore the biologic function of WISP3. Summary of article. Transgenic mice that broadly over-express WISP3 were created to search for in vivo biologic activities, since mice that lack WISP3 were normal. Surprisingly, transgenic mice were also phenotypically indistinguishable from wild-type animals. The mouse is a challenging model organism in which to explore the biologic function of WISP3.
authors.affiliation: Howard Hughes Medical Institute, Orthopaedic Research Laboratories, Department of Orthopaedic Surgery and Genetics, Children's Hospital and Harvard Medical School, Boston, MA, USA, yukio.nakamura@childrens.harvard.edu.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yajun
authors.initials: Y
authors.lastname: Cui
authors.forename: Carol
authors.initials: C
authors.lastname: Fernando
authors.forename: Wendy E
authors.initials: WE
authors.lastname: Kutz
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Warman