Analysis Tools
homeostasis/metabolism
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• males show a 26% increase in energy expenditure relative to wild-type controls
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• at 19 weeks of age, males show significantly increased transepidermal water loss relative to wild-type controls
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• mice show altered lipid composition in the skin
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• significant increase in sphingomyelin, dihydrosphingomyelin and hydroxyacylsphingomyelin levels relative to wild-type controls
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• at 9 weeks of age, males show a significant increase in total ceramide levels in the dorsal skin, tail epidermis and dermis relative to wild-type controls
• in dorsal skin, increased ceramide levels are noted in all ceramide species, with the greatest increase in C16:0, and not restricted to long-chain ceramides
• significant increase in ceramide content in the stratum corneum, as shown by increased total mean fluorescence intensity relative to wild-type controls
• significant increases in levels of monohexosylceramides, dihydroceramides, monohexodihydrosylceramides, phytoceramides, monohexosylphytoceramides, hydroxyacylceramides, and monohexosylhydroxyacylceramides
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• significant decrease in sphingosine, sphingosine-1-phosphate, dihydrosphingosine and dihydrosphingosine-1-phosphate levels relative to wild-type controls
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• males exhibit hypermetabolism with associated reduction of fat content during aging
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integument
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• significant increase in the number of cells expressing p63 (a marker for basal layer keratinocytes with proliferative capacity) in the dermis and epidermis at 27 weeks of age
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• mice display altered sebocyte arrangement and irregular nuclear shape relative to wild-type controls
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• gradual increase in the size of skin sebaceous glands (SGs) and the width of the infundibulum from 10 weeks, with SGs starting to fuse with the infundibulum by 16 weeks of age
• expansion of the sebaceous-hair follicle junctional zone marker Lrig1 beyond the junctional zone by 28 weeks of age
• marked alterations in sebocyte arrangement, lipid droplet structures and nuclear shapes relative to wild-type controls
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• gradual increase in the size of skin SGs from 10 weeks of age
• multiplication and enlargement of SG lobules by 28 weeks of age
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• at 19 weeks of age, males show significantly increased transepidermal water loss relative to wild-type controls
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• significantly increased levels of inflammatory infiltrate in the skin at 27 weeks of age, as determined by the number of CD45+ cells
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• dorsal coat anomalies (mixed length or long hair) are seen at P25 and become more obvious by 6 weeks of age
• at 10 weeks of age, mice show abnormalities in hair coverage that are more severe in males than in females
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• at 30 weeks of age, mutant hair shafts display compressed and smooth cuticles in awl hairs
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• although hair follicle cycling is normal at 6 weeks, follow-up 4 weeks later indicates that all mutant mice have regrown the hair following shaving, compared to only one of wild-type mice, suggesting disruption of the hair growth pattern
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• at 6-16 weeks of age, mice show a pattern of cyclical, sporadic hair loss followed by regrowth, consistent with cyclic alopecia
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• mice exhibit hair shaft cuticular abnormalities
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• unlike the scaly tile arrangement of the hair cuticle that covers the surface of wild-type hairs, mutant hair shafts display compressed and smooth cuticles in awl hairs, and a rough and irregular surface in zigzag hair shaft cuticles
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• at 30 weeks of age, mice display a rough and irregular surface in zigzag hair shaft cuticles
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• mutant hair follicles show expansion of the sebaceous-hair follicle junctional zone marker Lrig1 beyond the junctional zone by 28 weeks of age
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• mice show altered hair follicle patterning in the tail epidermis, with irregular arrangement of the hair follicle triplet clusters
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• mice show neutral lipids extending into the infundibulum with increasing age, as shown by oil red O staining
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• gradual increase in the width of the infundibulum from 10 weeks of age, with sebaceous glands starting to fuse with the infundibulum by 16 weeks of age
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• expansion of the hair follicle bulge domain at 28 weeks of age, as shown by K15 immunostaining
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• mildly increased dermal thickness at 16 weeks of age, mostly in the tail skin and to a lesser extent in the dorsal skin
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• ectopic localization of peroxisome proliferator activated receptor-gamma (Pparg) in the cornified layer of the epidermis at 16 weeks of age, unlike in wild-type controls
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• strong increase in the thickness of the cornified layer relative to wild-type controls, as shown by loricrin immunostaining in the tail skin
• however, no obvious changes are noted in the basal and granular layers of the epidermis
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• abnormal organization of the granular-transitional cell layer junctional area relative to wild-type controls
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• differences in the sizes of the keratohyalin granules in the granular layer relative to wild-type controls
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• hyperproliferation of both the dorsal and tail epidermis
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scaly skin
(
J:235775
)
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• increased incidence of scaly skin at 10 weeks of age
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• initiation of epidermal barrier formation is slightly delayed, as determined by toluidine blue dye exclusion assay; however, the barrier is fully formed and indistinguishable from wild-type by late E17.5-E18.5
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endocrine/exocrine glands
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• mice display altered sebocyte arrangement and irregular nuclear shape relative to wild-type controls
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• gradual increase in the size of skin sebaceous glands (SGs) and the width of the infundibulum from 10 weeks, with SGs starting to fuse with the infundibulum by 16 weeks of age
• expansion of the sebaceous-hair follicle junctional zone marker Lrig1 beyond the junctional zone by 28 weeks of age
• marked alterations in sebocyte arrangement, lipid droplet structures and nuclear shapes relative to wild-type controls
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• gradual increase in the size of skin SGs from 10 weeks of age
• multiplication and enlargement of SG lobules by 28 weeks of age
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adipose tissue
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• at 32 weeks but not at 9 weeks of age, males show a significant decrease in brown adipose tissue (BAT) weight relative to wild-type controls
• however, alterations in BAT are not associated with altered levels of UCP1
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• at 18 weeks of age, males show smaller lipid vacuoles within brown adipocytes relative to wild-type controls
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• at 32 weeks of age, males show a significant decrease in epididymal white adipose tissue (WAT) weight relative to wild-type controls
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• at 9 weeks of age, males show a small but significant increase in epididymal WAT weight relative to wild-type controls
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• at 32 weeks but not at 9 weeks of age, males show a significant decrease in inguinal WAT weight relative to wild-type controls
• however, no browning of WAT is detected, as UCP1 remains undetectable in inguinal WAT
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cellular
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• at 28 weeks of age, males show a significantly increased number of apoptotic (cleaved caspases-3-positive) cells in the skin relative to wild-type controls
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• significant increase in the number of cells expressing p63 (a marker for basal layer keratinocytes with proliferative capacity) in the dermis and epidermis at 27 weeks of age
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behavior/neurological
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• males show a 21% increase in food intake relative to wild-type controls
• however, the respiratory exchange ratio is normal
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• males show a 24% increase in total spontaneous activity relative to wild-type controls
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immune system
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• at 18 weeks of age, males show mildly increased eosinophilia relative to wild-type controls
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• significantly increased levels of inflammatory infiltrate in the skin at 27 weeks of age, as determined by the number of CD45+ cells
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growth/size/body
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• at 31-34 weeks of age, males show a significantly lower body weight than wild-type controls
• however, body weight is normal at 9 weeks of age
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hematopoietic system
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• at 18 weeks of age, males show mildly increased eosinophilia relative to wild-type controls
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