Читать книгу Pathology of Genetically Engineered and Other Mutant Mice - Группа авторов - Страница 59

Consomic strains have one intact chromosome from the donor strain transferred to a host background through repeated backcrossing, similar to congenic mice, but with careful screening at each generation for a fully intact specific donor chromosome. The strain nomenclature for consomic strains places the donor strain as a superscript to the transferred chromosome. The strain C57BL/6J‐Chr 1^PWD/Ph/Fore had Chromosome 1 from the inbred strain PWD/Ph bred onto a C57BL/6J host background by Dr. Jiri Forejt, whose laboratory code is Fore. A complete set of consomic strains, in which each chromosome from the donor strain is separately transferred to the same host background in a panel of separate strains, provides a unique tool for mapping mutations and modifiers.

These types of mice can be quite valuable when multiple congenic strains are created, each carrying the same single gene mutation. If each strain develops different lesions or different levels of severity of lesions, then one can integrate this type of strain into the analysis. For example, a spontaneous hypomorphic allele of laminin gamma 2 (Lamc2^jeb) resulted a model for non‐Herlitz Junctional Epidermolysis Bullosa, a blistering skin disease. Five congenic strains homozygous for this mutation revealed very different onset and severity of blistering disease and other lesions [30]. By crossing the congenic strains, several quantitative trait loci (QTLs) were identified, one major modifier gene on chromosome 19. By creating B6 and C57BL/6J‐Chr 19^PWD/Ph/ForeJ congenic strains that were both homozygous for Lamc2^jeb (on Chromosome 1), these mice could be crossed and each time rearrangements only occurred on Chromosome 19, thereby shortening the interval when selecting for disease severity. In so doing, it was possible to reduce the genetic interval to 1 megabase thereby identifying the binding region of Col17a1 as the major modifier gene [31].