The Foxn1‐dependent transcripts PCOLCE2 and mPPP1R16B are not required for normal thymopoiesis

Abstract

The adaptive immune system relies on the thymic microenvironment for the production of a diverse, self-tolerant T cell receptor repertoire. The central cellular organizer of the thymic microenvironment is the thymic epithelial cell (TEC). The development of TEC from endodermal precursor cells is under the control of the forkhead/winged helix transcription factor Foxn1 but the transcriptional program that leads to this unique epithelial differentiation has not been investigated functionally. Here, we show that expression of procollagen C-proteinase enhancer 2 (PCOLCE2) is absent in Foxn1-deficient TEC. In order to study the functional role of this gene in TEC differentiation, we have genetically inactivated PCOLCE2 and the gene encoding phosphatase 1 regulatory inhibitory subunit 16B (mPPP1R16B), another transcript lacking in Foxn1-deficient TEC. Mice deficient for either one or both of these transcripts presented a normal thymic microenvironment and undisturbed thymopoiesis. While there is no evidence for a functional role of PCOLCE2 and mPPP1R16B in thymus development, our results suggest that the lack of thymopoiesis in Foxn1-deficient mice is caused by multiple functional defects.

Effects of the absence of procollagen C-endopeptidase enhancer-2 on myocardial collagen accumulation in chronic pressure overload

“…PCOLCE-2 null (C57Bl6) mice were a kind gift of Drs. Conrad Bleul and Christiane Happe (Max-Planck Institute, Freiburg, Germany) (12). For in vivo studies, 25 PCOLCE2 null and 25 WT age-matched (3-5 mo, ϳequal representation of male and female banded) mice were subjected to PO induced by TAC.…”

Disruption of the murine procollagen C-proteinase enhancer 2 gene causes accumulation of pro-apoA-I and increased HDL levels

“…The PCPE2 gene-targeted mice were created ( 15 ) and maintained at the Max Planck Institute of Immunology and Epigenetics (Freiburg, Germany) according to protocols approved by the Institutional Animal Care and Use Committee of the Max Planck Institute of Immunobiology and Epigenetics. Mice were maintained on a 12 h light/dark cycle and fed either a rodent chow or high-fat diet (Harlan Teklab).…”

“…While several studies have been published addressing the physiological role of PCPE1 ( 13,14 ), the function of PCPE2 remains unclear. PCPE2-defi cient (PCPE2 KO) mice are viable and fertile, and they do not show gross developmental abnormalities ( 15 ). Very recently, a series of biochemical experiments ( 10 ) sparked interest in PCPE2 when an important role for this protein in apoA-I synthesis and HDL metabolism was described.…”

Procollagen C-endopeptidase Enhancer Protein 2 (PCPE2) Reduces Atherosclerosis in Mice by Enhancing Scavenger Receptor Class B1 (SR-BI)-mediated High-density Lipoprotein (HDL)-Cholesteryl Ester Uptake

“…Animals and Diets-PCPE2-deficient mice in the C57BL/6 background were obtained from the Max Planck Institute (43) and then crossed with LDLr Ϫ/Ϫ mice to generate LDLr Ϫ/Ϫ , PCPE2 Ϫ/Ϫ mice. Both LDLr Ϫ/Ϫ and LDLr…”

“…Studies in PCPE2 Ϫ -deficient mice provide the first direct experimental evidence linking PCPE2 to HDL metabolism (43). PCPE2 knock-out mice had elevated concentrations of enlarged plasma HDL (44), despite displaying defective ABCA1-mediated cholesterol efflux capacity.…”