Table 1 Summary of PGRN KO mouse lines and their endo-lysosomal and immune cell phenotypes

Grn KO (Nishihara)

Targeted deletion of exons 2–13 of Grn gene [209]

• Increase in Lyz2 and Ctsz in hippocampus with LPS treatment [197]

• Increased Lamp1 + and mature CtsD + in immortalized cell lines and primary microglia [73]

• Increased LAMP1, saposin D, CTSD, and TMEM106b in whole brain lysate [199]

• Increased autofluorescent material in retinal lysosomes [200]

• Age-dependent increase in Lamp1 + and p62 + staining, Tfeb, CtsD, and Atp6v0d2 transcript, and autofluorescent signal in cortex, thalamus, and VPM/VPL [201]

• Increased Cd63, Cd68, Hexb, and Ctsd expression in brain [202]

• LPS-mediated increase in Cd68 + staining, increase in Mpeg1, Il-1b, and mPges-1 in hippocampus [197]

• Increase in IBA1 + cells around choroidal neovascularization lesion. Increase CD68 + macrophage cell line in laser-irradiated RPE–choroid complex [198]

• Age-dependent increase in Iba1 + and Cd68 + cells. Increase in Tnf, Mpeg1, Cyba, Cybb, C4, and Lcn2 expression in cortex, thalamus and VPM/VPL [201]

• Increased serum Il-6, Il-10, and MCP1 after LPS, Decreased Listeria/Lc3 co-localization in Grn KO BMDM [128]

Grn KO (Ding)

Targeted deletion of exons 1–4 of Grn gene [99]

• Prosaposin trafficking defects in immortalized cell lines and brain [35]

• Age-dependent increase in Gpnmb and Galectin-3, primarily on microglia [17]

• Increased Galectin-3 +, Plin2 +, and lipofuscin accumulation in response to demyelination in brain [205]

• Increased Lamp1 +, Cathepsin D +, and lipofuscin accumulation [206]

• Decreased abundance of BMP species, age-dependent increase in glucosylsphingosine and decrease in GCase activity in brain and BMDM [207]

• Increased Tnf, Il-6, and iNos and decreased Il-10 after spinal cord injury [203]

• Increased Tnf, Il-6, and Il-1b after LPS treatment in macrophages [99]

• Increase Tnf, Il-6, and Il-1b after LPS injection, increased immune cell infiltration into lungs during LPS treatment [204]

• Age-dependent increase in plasma Gpnmb ECF [17]

• Increased Iba1 +, Gpnmb +, and Trem2 + staining in response to demyelination in brain [205]

• Increased Iba1 +, Gfap +, and Cd68 + [206]

• Sex-dependent effects in immune cells: increase in Ly6C high monocytes in blood, decrease of MHCII expression in microglia, increase in CD8 + T cells in both blood and brain, altered CD44 expression on T-cell populations [100]

Grn R493X (knock-in)

Knock-in of R504X Grn gene; mimics the R493X GRN mutation, positive for nonsense-mediated decay [153]

• Altered ganglioside metabolism and decreased BMP levels in brain [82]

• Increased cathepsin D expression, higher Lc3II/LC3I ratio in brain [154]

• Increased Iba1 +, GFAP +, and C1q + staining in brain [154]

• Age-dependent increase Il-1b, Tnf, and Mcp1 transcript [208]

Floxed Grn

loxP sites flanking the Grn coding sequence; complete removal of Grn gene when crossed with Cre line, allows for cell-specificity [150]

• Altered lipidomic profile with successive loss of Grn alleles. Increased expression of Ctsd, Cd68, and Lyz2, and Increased number and size of lysosomes in neurons [83]

• Increased β-Gal, β-Hex, HexA, GLA and GCase activity [78]

• Age-dependent increase in pro- and mature CstD and Lamp1 [211]

• Increased mRNA of Tnf, Il-1b, and Il-6; decreased Il-10 [150]

• Increased expression of Trem2 and Tyrobp [83]

• Increased Iba1 + and Gfap + staining in the hippocampus, cortex, and thalamus [152]

• Increased Iba1 + staining in the thalamus [210]