It is increasingly recognized that young,chow-fed inbred mice poorly model the com-plexity of human carcinogenesis.In humans,age and adiposity are major risk factors for malignancies,but most genetically engineered mo...It is increasingly recognized that young,chow-fed inbred mice poorly model the com-plexity of human carcinogenesis.In humans,age and adiposity are major risk factors for malignancies,but most genetically engineered mouse models(GEMM)induce car-cinogenesis too rapidly to study these influences.Standard strains,such as C57BL/6,commonly used in GEMMs,further limit the exploration of aging and metabolic health effects.A similar challenge arises in modeling periodontitis,a disease influenced by aging,diabesity,and genetic architecture.We propose using diverse mouse popula-tions with hybrid vigor,such as the Collaborative Cross(CC)×Apc ^(Min) hybrid,to slow disease progression and better model human colorectal cancer(CRC)and comorbidi-ties.This perspective highlights the advantages of this model,where delayed car-cinogenesis reveals interactions with aging and adiposity.Unlike Apc ^(Min) mice,which develop cancer rapidly,CC×Apc ^(Min) hybrids recapitulate human-like progression.This facilitates the identification of modifier loci affecting inflammation,diet susceptibility,organ size,and polyposis distribution.The CC×Apc ^(Min) model offers a transformative platform for studying CRC as a disease of adulthood,reflecting its complex inter-play with aging and comorbidities.The insights gained from this approach will en-hance early detection,management,and treatment strategies for CRC and related conditions.展开更多
基金Israel Cancer Research FoundationSamuel Waxman Cancer Research FoundationCore funding from Tel Aviv University。
文摘It is increasingly recognized that young,chow-fed inbred mice poorly model the com-plexity of human carcinogenesis.In humans,age and adiposity are major risk factors for malignancies,but most genetically engineered mouse models(GEMM)induce car-cinogenesis too rapidly to study these influences.Standard strains,such as C57BL/6,commonly used in GEMMs,further limit the exploration of aging and metabolic health effects.A similar challenge arises in modeling periodontitis,a disease influenced by aging,diabesity,and genetic architecture.We propose using diverse mouse popula-tions with hybrid vigor,such as the Collaborative Cross(CC)×Apc ^(Min) hybrid,to slow disease progression and better model human colorectal cancer(CRC)and comorbidi-ties.This perspective highlights the advantages of this model,where delayed car-cinogenesis reveals interactions with aging and adiposity.Unlike Apc ^(Min) mice,which develop cancer rapidly,CC×Apc ^(Min) hybrids recapitulate human-like progression.This facilitates the identification of modifier loci affecting inflammation,diet susceptibility,organ size,and polyposis distribution.The CC×Apc ^(Min) model offers a transformative platform for studying CRC as a disease of adulthood,reflecting its complex inter-play with aging and comorbidities.The insights gained from this approach will en-hance early detection,management,and treatment strategies for CRC and related conditions.
