The Pathology of Aging 129S6/SvEvTac Mice

Abstract

The 129 mouse strain is commonly used for the generation of genetically engineered mice. Genetic drift or accidental contamination during outcrossing has resulted in several 129 substrains. Comprehensive data on spontaneous age-related pathology exist for the 129S4/SvJae substrain, whereas only limited information is available for other 129 substrains. This longitudinal aging study describes the life span and spontaneous lesions of 44 male and 18 female mice of the 129S6/SvEvTac substrain. Median survival time was 778 and 770 days for males and females, respectively. Tumors of lung and Harderian gland were the most common neoplasms in both sexes. Hepatocellular tumors occurred mainly in males. Hematopoietic tumors were observed at low frequency. Suppurative and ulcerative blepharoconjunctivitis was the most common nonneoplastic condition in both sexes. Corynebacteria (primarily Corynebacterium urealyticum and C. pseudodiphtheriticum) were isolated from animals with blepharoconjunctivitis and in some cases from unaffected mice, although a clear causal association between corynebacterial infections and blepharoconjunctivitis could not be inferred. Polyarteritis occurred only in males and was identified as the most common nonneoplastic contributory cause of death. Eosinophilic crystalline pneumonia occurred in both sexes and was a relevant cause of death or comorbidity. Epithelial hyalinosis at extrapulmonary sites was noted at higher frequency in females. This study contributes important data on the spontaneous age-related pathology of the 129S6/SvEvTac mouse substrain and is a valuable reference for evaluation of the phenotype in genetically engineered mice obtained with this 129 substrain.Keywords 129 mouse, aging, blepharoconjunctivitis, Harderian gland, hyalinosis, phenotyping Each inbred laboratory mouse strain exhibits a unique spectrum of naturally occurring lesions that develop progressively with age. Crosses of different strains usually result in variations of the original strain-specific phenotype, which include vanishing, attenuation, or exacerbation of expected lesions or even development of completely new conditions. 20,72 In this context, an accurate definition of strain-specific pathology in those inbred mice that are most frequently used in biomedical research (especially for the generation of genetically engineered mice) is crucial to understand whether a phenotype results from the experimental intervention or rather reflects a naturally occurring entity. 3,54,62 In addition, longitudinal survival studies determining the aging phenotype of inbred strains are particularly important, as they provide a useful reference that enables the selection of the most appropriate genetic background for specific experiments and facilitates the interpretation of clinicopathologic changes that develop in long-term studies. 3,45,72 Thorough and comprehensive pathologic analysis of inbred strains is important not only for interpreting lesions in the setting of hypothesis-driven research but also for large-sc...

Pathology of Aging in NODscidgamma Female Mice

“…AMP was identified in a few animals. AMP has been originally described in Swiss mice 18 and in mice with a Swiss background; 43 it has been reported as a major cause of disease and death in 129S4/SvJae 23 and 129S6/SvEvTac mice, 51 while it has been less commonly observed in B6;129 mice 7,20 and C57BL/6 J. 7 In our study, this finding was only sporadic, focal, and minimal to mild in severity.…”

A polymorphism in the tumor suppressor p53 affects aging and longevity in mouse models

“…In 129SV sl mice, P72 mice showed an overall longer lifespan compared with R72 mice; the median survival age was 759 days for P72 mice and 697 days for R72 mice, respectively (Log-rank test: p<0.0001) ( Figure 1A ). The causes of death included tumor, inflammation (including dermatitis), ocular lesion, urinary syndrome, nephropathy, etc., which are common causes of death in 129SV sl mice as reported by previous studies ( Marx et al, 2013 ; Brayton et al, 2012 ; Radaelli et al, 2016 ) ( Table 1 ). For those mice died from non-neoplastic events, P72 mice showed a significantly longer lifespan than R72 mice; the median survival was 768 days for P72 mice and 673 days for R72 mice, respectively (Log-rank test: p<0.0001) ( Figure 1B ).…”

Spontaneous Incidental Brain Lesions in C57BL/6J Mice

“…Definition of the background or incidental lesions associated with a specific mouse strain is vital to the correct interpretation of pathological endpoints in the experimental context. 10,30,60,62 C57BL/6J is arguably the most common inbred mouse strain employed in biomedical research, representing the reference congenic/consomic background to generate mouse lines harboring both spontaneous and genetically engineered mutations. 67 C57BL/6J also represents the preferred congenic background for numerous mutant models of neurological conditions, including important neurodegenerative disorders and brain tumors.…”