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Published on: May 1, 2015
Histopathology of lymphatic tissues in transgenic mice expressing human tissue kallikrein gene
1Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston.
Background:
Tissue kallikrein is a member of a family of closely related serine proteinases whose genetics are currently under intense investigation, but whose functions are still poorly understood. Functions of human tissue kallikrein, other than production of inflammatory kinins, are not readily amenable to investigation. A current mechanism for examining the function of a gene product is to introduce the gene with tissue-specific and/or inducible promoters into a suitable host that can then be experimentally manipulated.
Experimental Design:
Five transgenic mouse lines were established by backcross matings of transgenic founder mice containing the human tissue kallikrein gene. The inserted genomic material included the full-length kallikrein coding sequence as well as 800 bp in the upstream promoter region and 300 bp in the 3' noncoding region (PHK). Two of the five strains contained, in addition to the complete coding region and 3' flanking sequence, an upstream, zinc-inducible metallothionein promoter (MRE-PHK). Tissues from animals containing human kallikrein gene constructs (as determined by Southern blot of tail DNA) were examined histologically, and compared with control tissues from siblings negative for the gene.
Results:
Transgenic mice exhibited tissue pathology in several lymphatic organs. Cytoarchitecture was disrupted in both thymus and spleen. The distinction between cortex and medulla in the thymus was usually blurred, and cytolysis was common. Spleens exhibited decreased T cell-dependent zones (periarteriolar sheath), with active hematopoietic foci throughout the red pulp. In lymph nodes, cortical nodules were rare. The deep cortex (paracortical area) was usually normal in heterozygotes, but often depleted in homozygous animals. Comparable results were obtained in all five transgenic strains.
Conclusions:
Expression of human tissue kallikrein appears to exert a profound effect on the cytoarchitecture of lymphatic tissues and a general decrease in lymphocytes, particularly in T cell-dependent areas. These findings presumably reflect altered function of lymphatic tissues in transgenic mouse strains carrying the human kallikrein gene.
