Ectopic expression of Col2.3 and Col3.6 promoters in the brain and association with leptin signaling

Erica L. Scheller, Gina M. Leinninger, Kurt D. Hankenson, Martin G. Myers, Paul H. Krebsbach

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The collagen 2.3 and 3.6 promoters have been used to drive Cre expression for generation of conditional transgenic mutant mice. Within the bone, Col3.6 is expressed by mesenchymal precursor cells and their downstream progeny, while Col2.3 is more osteoblast specific. Our generation of transgenic mice with Col2.3-Cre- and Col3.6-Cre-driven deletion of the long-form leptin receptor (ObRb) necessitated a thorough analysis of the nonspecific expression of these promoters in the central nervous system. Both Col2.3 and Col3.6 were capable of forcing loxP recombination in the brain as demonstrated by EGFP expression in ROSA reporter mice. Expression of Col2.3 was limited to the central base of the brain near the third ventricle. In contrast, robust expression of Col3.6 was noted throughout the brain, centering near the distal third ventricle, third ventricle, and aqueduct. We subsequently analyzed the colocalization of leptin-responsive P-Stat3 neurons with Col3.6-expressing neurons. Approximately 5-10% colocalization was noted in leptin-responsive brain areas such as the arcuate nucleus, dorsal medial hypothalamus, ventral premammillary nucleus, and lateral hypothalamus. Injection of 3.6 Cre+F/F ObRb knockout mice with leptin confirmed the presence of an intact P-Stat3 response that was dampened in the lateral hypothalamus (p < 0.050). This test was done to explore the contribution of neural leptin signaling to the bone phenotype of the 3.6 Cre+F/F mice. Our analysis indicates that neural ObRb deletion, while present, is likely not the sole driver of femoral changes through traditional sympathetic circuits.

Original languageEnglish
Pages (from-to)268-273
Number of pages6
JournalCells Tissues Organs
Volume194
Issue number2-4
DOIs
StatePublished - Aug 2011

Keywords

  • Bone
  • Brain
  • Collagen promoter
  • Leptin
  • Leptin receptor

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