Table 1

Functions of Jun and Fos proteins

Activator protein 1 protein

Phenotype

Affected organs/cells


Transgenic

H2Kb-Jun

None

None

Ubiquitin C-JunBa

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-2a

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-creERTJunB + 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.

Zenz et al. Arthritis Research & Therapy 2008 10:201   doi:10.1186/ar2338