CSF-deficient mice--what have they taught us?
Haemopoietic growth factor-deficient mice have been particularly instructive for defining the usual physiological role of these factors. Mice now exist lacking the granulopoietic factors G-CSF, GM-CSF, M-CSF (CSF-1), SCF, several other factors influencing haemopoiesis (including erythropoietin, interleukins 5 and 6), combinations of these factors (GM- & M-CSF; G- & GM-CSF; G- & GM- & M-CSF) and several CSF receptor components. Most of these mice were generated by targeted gene disruption, others are spontaneously arising mutants. The phenotypes of these mice indicate that the granulopoietic factors have both unique and redundant roles in vivo. Some factors are uniquely important in baseline myelopoiesis. Experimental infection of CSF-deficient mice indicates unique roles for some factors in emergency 'overdrive' haemopoiesis. Recovery from myeloablation evaluates the role of CSFs in emergency 'restoring normality' haemopoiesis. Redundancy also exists in the capacity of CSFs to support complete granulocyte development in vivo. Some factors are not involved in all the in vivo roles suggested by the range of their actions demonstrable in vitro. Some CSFs have indispensable roles in non-haemopoietic tissues. Some factors have in vivo roles not anticipated from previous studies. Mice deficient in several factors have identified compensating roles for factors by revealing exacerbated and additional phenotypic features, and may unmask additional in vivo roles.
Lieschke
G J
GJ
Whitehead Institute for Biomedical Research, Cambridge, MA 02142-1479, USA.
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D003115:Colony-Stimulating Factors / Q000172:deficiency*; D004920:Erythropoiesis; D005854:Germ Cells / Q000166:cytology; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis; D008171:Lung Diseases / Q000209:etiology; D051379:Mice; D018345:Mice, Knockout; D012880:Skin Pigmentation
D003115:Colony-Stimulating Factors