Practical pathology of aging mice

Abstract

Old mice will have a subset of lesions as part of the progressive decline in organ function that defines aging. External and palpable lesions will be noted by the research, husbandry, or veterinary staff during testing, cage changing, or physical exams. While these readily observable lesions may cause alarm, not all cause undue distress or are life-threatening. In aging research, mice are maintained until near end of life that, depending on strain and genetic manipulation, can be upwards of 33 months. Aging research has unique welfare issues related to age-related decline, debilitation, fragility, and associated pain of chronic diseases. An effective aging research program includes the collaboration and education of the research, husbandry, and veterinary staff, and of the members of the institution animal care and use committee. This collaborative effort is critical to humanely maintaining older mice and preventing excessive censorship due to non-lethal diseases. Part of the educational process is becoming familiar with how old mice appear clinically, at necropsy and histopathologically. This baseline knowledge is important in making the determination of humane end points, defining health span, contributing causes of death and effects of interventions. The goal of this paper is to introduce investigators to age-associated diseases and lesion patterns in mice from clinical presentation to pathologic assessment. To do so, we present and illustrate the common clinical appearances, necropsy and histopathological lesions seen in subsets of the aging colonies maintained at the University of Washington.

Inbred mouse strains reveal biomarkers that are pro‐longevity, antilongevity or role switching

“…The latter reflect ‘inflamm-aging’ as described. We note that such chronic inflammatory processes are common to aging mice (Ray et al ., 2010; Pettan-Brewer & Treuting, 2011), consistent with similar findings in aging humans (Krabbe et al ., 2004). Elevation of neutrophil numbers in younger mice may be due to several specific causes, see the Appendix S1 Discussion.…”

The Pathology of Aging 129S6/SvEvTac Mice

“…We hypothesize that age-related structural and/ or functional changes in the eyelids and lacrimal system may have impaired the integrity of the mucocutaneous epithelial barrier, thus promoting chronic inflammation and facilitating the colonization of the palpebral conjunctiva by commensal bacteria normally residing on the skin. 33,43,45 Further supporting this view, anterior migration of the palpebral mucocutaneous junction represents a well-documented age-related condition in mice where it is mainly associated with eyelid laxity and meibomian gland atrophy and dysfunction. 42,61 Furthermore, our data suggest that concurrent Harderian gland tumors contribute significantly to the exacerbation, rather than to the onset, of blepharoconjunctivitis.…”

Spontaneous Histologic Lesions of the Adult Naked Mole Rat (Heterocephalus glaber)

“…5, 6). 1,81 Age-associated heart lesions included cardiac karyomegaly and megalocytosis (Fig. 11) in addition to arteriosclerosis, myocyte degeneration, and fibrosis.…”

“…12,81 Therefore, the proliferative splenic lesion was particularly intriguing, in which the increased cellularity of splenic lymphoid follicles (Figs. 15, 16) could have been considered an incipient follicular lymphoma.…”