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Frailty Assessment in an Aging Mouse Model
Published on: September 23, 2025
Skin fragility in the wild-derived, inbred mouse strain Mus pahari/EiJ
C Herbert Pratt1, Christopher S Potter1, Raoul V Kuiper2
1The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609-1500, USA.
Abstract:
Mus pahari is a wild-derived, inbred mouse strain. M. pahari colony managers observed fragility of this strain's skin resulting in separation of tail skin from the mouse if handled incorrectly. Tail skin tension testing of M. pahari resulted in significantly lowered force threshold for caudal skin rupture and loss in comparison to closely related inbred mouse species and subspecies and even more than a model for junctional epidermolysis bullosa. Histologically, the tail skin separated at the subdermal level with the dermis firmly attached to the epidermis, excluding the epidermolysis bullosa complex of diseases. The dermal collagen bundles were abnormally thickened and branched. Elastin fiber deposition was focally altered in the dermis adjacent to the hair follicle. Collagens present in the skin could not be differentiated between the species in protein gels following digestion with pepsin. Together these data suggest that M. pahari have altered extracellular matrix development resulting in separation of the skin below the level of the dermis with moderate force similar to the African spiny mouse (Acomys spp.).
Insights
The wild-derived mouse strain Mus pahari exhibits fragile skin, leading to tail skin separation. This fragility stems from altered extracellular matrix development, impacting collagen and elastin in the dermis.
Area of Science:
- Genetics and Genomics
- Dermatology
- Comparative Biology
Background:
- The wild-derived inbred mouse strain, Mus pahari, displays unusual skin fragility.
- Colony managers noted that improper handling can cause tail skin separation in M. pahari.
- This phenotype is more severe than in other related mouse strains and even models of junctional epidermolysis bullosa.
Purpose of the Study:
- To investigate the underlying cause of skin fragility and tail skin separation in Mus pahari.
- To characterize the histological and molecular basis of the observed phenotype.
- To compare the skin properties of M. pahari to other mouse strains and related species.
Main Methods:
- Tail skin tension testing to measure force thresholds for skin rupture.
- Histological examination of tail skin sections.
- Biochemical analysis of skin collagen using protein gels and pepsin digestion.
Main Results:
- Mus pahari exhibited a significantly lower force threshold for caudal skin rupture compared to control groups.
- Histological analysis revealed skin separation at the subdermal level, with abnormal thickening and branching of dermal collagen bundles.
- Elastin fiber deposition was focally altered near hair follicles, but collagen composition appeared similar across species.
- The separation mechanism excluded the typical features of epidermolysis bullosa.
Conclusions:
- Mus pahari possesses an altered extracellular matrix development, leading to its characteristic skin fragility.
- The observed phenotype involves subdermal skin separation, distinct from epidermolysis bullosa.
- This condition shares similarities with the skin properties of the African spiny mouse (Acomys spp.).
