Umod-KO Mouse

Umod, which codes for uromodulin (also known as Tamm-Horsfall protein), is a kidney-specific gene. Uromodulin is the most abundant protein excreted in normal urine and has specific biochemical properties that mediate important functions in the kidney and urine. It is involved in various kidney-related biological processes and its genetic variation is relevant to the pathogenesis and prognosis of kidney diseases [1,3].

Mutations in Umod are the major cause of autosomal dominant tubulointerstitial kidney disease (ADTKD), which leads to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Different types of Umod mutations exist, from rare large-effect variants causing ADTKD to common low-impact variants associated with kidney function and CKD risk in the general population, and even intermediate-effect variants. For example, the p.Thr62Pro missense variant in Umod shows incomplete penetrance, a high genetic load in familial CKD clusters, and is associated with kidney failure. Carriers of this variant display reduced disease severity, slower CKD progression, and intermediate reduction of urinary uromodulin levels [2,4].

In conclusion, Umod is crucial for normal kidney function, and its mutations are significantly associated with kidney diseases such as ADTKD and CKD. Studies on Umod-related mutations in different populations help to understand the genetic architecture of these kidney diseases, providing insights into disease mechanisms and potentially guiding the development of diagnostic and treatment strategies.