Activator protein 1 (Fos/Jun) functions in inflammatory bone and skin disease

Table 1 Functions of Jun and Fos proteins

Activator protein 1 protein	Phenotype	Affected organs/cells
Transgenic
H2Kb-Jun	None	None
Ubiquitin C-JunB^a	Increased bone mass	Not defined
CD4-JunB	Enhanced T helper cell 2 maturation	Thymus, CD4 thymocytes
Ubiquitin C-JunD	Peripheral T cells and B cells reduced	Lymphocytes
H2Kb-Fos	Osteosarcoma	Bone, osteoblasts
H2Kb-Fos/Rsk-2^-/y	Reduced osteosarcoma	Bone, osteoblasts
H2Kb-FosB	None	Bone
TCRβ-ΔFosB	Impaired T cell differentiation	Thymus, immature thymocytes
NSE-ΔFosB	Osteosclerosis	Bone, osteoblasts
H2Kb-Fra-1	Osteosclerosis	Bone, osteoblasts
CMV-Fra-2	Occular malformations	Anterior eye structure
H2Kb-Fra-2^a	Increased bone mass, fibrosis	Bone, internal organs, skin
Knockout
Jun	Embryonic lethal on embryonic day 12.5	Liver, heart, neural crest
JunB	Embryonic lethal on embryonic day 10	Extraembryonic tissues
JunD	Male sterility	Testis, spermatides
c-Fos	Osteopetrosis	Bone, osteoclasts
FosB	Nurturing defect	Brain, hypothalamus
Fra-1	Embryonic lethal on embryonic day 9.5	Extraembyonic tissue
Fra-2	Lethal at birth	Bone, osteoclasts
Conditional
Alfp-cre Jun	Liver regeneration defect	Liver, hepatocytes
Col2a1-cre Jun	Scoliosis	Bone, notochordal cells
Nestin-cre Jun	Axonal regeneration defect	Central nervous system, motoneurons
MORE-cre JunB	Osteopenia	Bone, osteoclasts, osteoblasts
K5-cre Jun	Eyes open at birth, reduced skin tumors	Keratinocytes
Nestin-cre Fos	Learning defects	Brain, hippocampal neurons
MORE-cre Fra-1	Osteopenia	Bone, osteoblasts
Inducible
K5-creER^TJunB + Jun	Psoriasis-like disease	Skin, joints, keratinocytes

Knockout, conditional knockout and gain of function (transgenic) approaches applied to study the role of Jun and Fos proteins during development and in diseases. The gain-of-function approaches were performed with different promoters, either leading to ubiquitous expression (for example, H2Kb, ubiquitin C, or cytomegalovirus (CMV)) or to tissue-specific expression (for example, CD4, TCRβ, or neuron-specific enolase (NSE)) of the transgenes. ^aUnpublished data from the Wagner Laboratory.