Table 1.

Summary of C/EBPδ knockout mouse phenotypes. Only reports with in vivo studies (i.e., not those using only cultured cells) are included.

Primary organ and cell type(s)	Main loss of function phenotype	Affected Gene(s)#	Strain background	References
Adipocytes	Exacerbated impairment of adipocyte differentiation due to C/EBPβ null mutation	Ucp1↓	Mixed C57BL6x 129/Ola	44
Adipocytes	Reduced body and fat mass index specifically in females*	-	Mixed 129S1xC57BL6 (F2)	81
CNS, dendritic cells	Less severe clinical score for experimental autoimmune encephalomyelitis	Il10↑	C57BL/6	126
Brain, glia	Reduced LPS response	Tnfa↓ Il6↓ Il1b↓	C57BL/6	127
Brain	Enhanced learning by contextual fear conditioning	-	Mixed 129S1xC57BL6	45
Peripheral motor neurons	Impaired regeneration after sciatic nerve injury	Sprr1a↓	C57BL/6	163
Tumor implant, lymphendothelial cells	Impaired lymphangiogenesis in grafted tumors	Vegfc↓ Vegfr3↓	C57BL/6	48
Systemic inflammatory, macrophages	Decreased collagen-induced arthritis	Ccl20↓ Cxcl1↓ Il23a↓ Tnfaip6↓	C57BL/6	164
Systemic, inflammatory	Reduced LPS responses and increased survival	Systemic: IL-6↓** TNFα↓	C57BL/6	122
Systemic, macrophages	Impaired clearance, specifically of high titer E. coli infections	Il6, Saa3, Cxcl2 and others↓	C57BL/6	21
Lung, macrophages	Reduced macrophage infiltration and clearance of Klebsiella infection**	Systemic Il-6↑ TNF-α↑	C57BL/6	75
Lung, epithelial and inflammatory cells	Relative resistance to pneumococcal pneumonia**	Pafr↓	C57BL/6	120
Lung, macrophages	Reduced LPS-induced lung injury	Lung: Il-6, TNF-α, MIP-2 ↓	C57BL/6	82
Kidney	Reduced kidney damage after renal ischemia/reperfusion injury**	Systemic TNFα↓ IL-6↓	C57BL/6	122
Kidney, tubular cells	Reduced renal absorption of lactate and urate	Slc5a8↓ Slc5a12↓	C57BL/6	165
Kidney, mesangial cells	Reduced experimental glomerulonephritis	Acta2↓	129	166
Mammary gland	Delayed cell death and involution after lactation##	Tp53↓ Bcl2a1↓ Igfbp5↓ Ccnd1↑ Survivin↑	C57BL/6	70
Mammary gland, tumor	Increased MMTV-Neu mammary tumor multiplicity and reduced lung metastases, impaired hypoxia adaptation	Fbxw7a↑ Cxcr4↓	FVB/N	34
Mammary gland, tumor; peritoneal macrophages	Reduced LPS response	Fbxw7a↑ Tlr4↓	FVB/N	57
Mammary gland	Increased ductal branching in aged mice ***	-	Mixed 129S1xC57BL6	90
Negative Results:
Ovary, theca/interstitial cells	Not essential despite LH-induced expression	-	129S1	71
Bone	Normal bone density	-	Mixed 129S1xC57BL6 (F2)	81
Mammary gland	Morphologically normal involution##	Trpm2↓ Igfbp5↓	Mixed 129S1xC57BL6	90
Lung, macrophages	Normal inflammatory response to IgG	-	C57BL/6	83

^#This column highlights some of the genes/proteins whose expression is regulated directly or indirectly by C/EBPδ. See citations for details.

^## Note contradictory results of ⁹⁰ and ⁷⁰, possibly due to strain background.

*This phenotype was not observed previously in a study using the same strains ⁴⁵, nor in studies using mice backcrossed to C57BL/6 ⁷⁰, 129S1 ⁷¹, or FVB/N strains ³⁴. We speculate that the reduced body mass of C/EBPδ null female mice may be due to a maternal/paternal effect, because only this study ⁸¹ used compound C/EBPδ and C/EBPβ heterozygous breeders.

** Controls were not from the same cross as mutants.

***This phenotype was not observed in mice backcrossed to the C57BL/6 or FVB/N strain background (70, and unpublished data) and may therefore be specific to the mixed strain background.