A GFP-neo cassette replaces exons 3-4, including the initiation sequence, of the Eph receptor B6 (Ephb6) gene, abolishing gene function. EPHB6 is a transmembrane cell surface receptor tyrosine kinase expressed on the surface of T cells, leukemic cells, vascular smooth muscle cells (VSMC), the adrenal gland medulla, skin, teeth, tongue and many brain regions. Homozygous Ephb6-/- mice are viable and fertile. Decreased EPHB6 expression occurs in mature T cells. Weak GFP fluorescence, driven by the Ephb6 promoter, is visible on the surface of CD4+CD8+ DP, CD4+ SP, and CD8+ SP thymocytes from Ephb6-/- mice. T cells from these mice show reduced expression of interleukin (IL)-2, IL-4, and interferon-γ, and have compromised responses upon activation. These mice also exhibit diminished responses to both delayed-type hypersensitivity and induced experimental autoimmune encephalitis (EAE). Small arteries from male Ephb6-/- mice display reduced contractility, while small arteries from female and castrated male Ephb6-/- mice show increased contractility. Male Ephb6-/- mice present reduced 24-h urine catechoamine excresion. Male Ephb6-/- mice present reduced 24-h urine catechoamine excresion. Levels return to normal following castration. Castrated Ephb6-/- males have increased systolic and diastolic blood pressure.
