Some investigators have performed focused comparisons between gene-disease associations emerging from GWAS and the mouse phenotypes observed when the respective gene loci are knocked out [5], [6].
While OGR1 deficiency did not result in a strong phenotype by itself, it may generate interesting and strong phenotypes when mice are challenged, as we report here for melanoma cells.
Therefore, it is yet to be established whether there are categories of lncRNAs that are more likely to manifest in phenotypes when disrupted in mouse.
The MGI list consisted of human genes whose mouse orthologs are associated with abnormal placental phenotypes when disrupted.
We observe similar phenotypes when we reduce Tcf7l2 expression from high to normal levels in our mice.
Lexicon's KO mice did not have an obesity phenotype when fed mouse chow or high fat diet (data not shown) but subcutaneous fat was not examined.
A putative biomarker was considered 'more relevant' or 'more promising' when a knockout mouse phenotype provided supportive evidence that the gene or protein speculated to be a biomarker displayed a phenotype that would be in line with the putative role of that gene or protein in the pathophysiology process modeled.
Muc1 knockout mice (Muc1-/; MUC1 is human; Muc1 is mouse) show a reduction in tumorigenic phenotype when crossed onto mice overexpressing the Wnt-1 [ 7] or polyomavirus middle T antigen [ 8] oncogenes in the mammary gland.
We have not investigated here the role of CCR5 to infection outcome but it is clear that CCR1 /– mice had no major phenotype when infected with an inoculum which causes severe disease in mice.
In a recent study, it was reported that while Il1r1−/− and Casp1−/− mice developed fewer tumors and had delayed tumor incidence compared to WT mice in a chemical-induced skin cancer model, Asc−/− mice had no discernible phenotype when compared to WT animals.
