skeleton
• by 10 months of age, homozygotes show 5-fold increase in bone marrow osmium-stained lipid volume within the decalcified proximal tibia relative to wild-type controls, indicating pathological marrow adipose tissue (MAT) expansion
• however, bone marrow adiposity is normal at 2 and 6 months of age, and bone marrow cellularity is not significantly reduced at 10 months of age despite MAT expansion
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• by 10 months of age, homozygotes exhibit a 5-fold increase in bone marrow fat volume relative to wild-type controls
• however, MAT expansion is not coincident with bone loss or excess peripheral adiposity
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• at 2 and 6 months of age, homozygotes show a significant reduction in trabecular bone mineral density (BMD) relative to wild-type controls
• however, no significant differences are noted in trabecular BMD at 10 months of age
• cortical BMD is normal at all ages and unchanged by MAT expansion
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• at 2 and 6 months of age, homozygotes show a significant reduction in the ratio of trabecular bone volume to total volume (BV/TV) relative to wild-type controls
• however, this phenotype does not progress with age or MAT expansion
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adipose tissue
• by 10 months of age, homozygotes show 5-fold increase in bone marrow osmium-stained lipid volume within the decalcified proximal tibia relative to wild-type controls, indicating pathological marrow adipose tissue (MAT) expansion
• however, bone marrow adiposity is normal at 2 and 6 months of age, and bone marrow cellularity is not significantly reduced at 10 months of age despite MAT expansion
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• by 10 months of age, homozygotes exhibit a 5-fold increase in bone marrow fat volume relative to wild-type controls
• however, MAT expansion is not coincident with bone loss or excess peripheral adiposity
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• at 2 months of age, gonadal fat pad mass is only modestly increased by 15% relative to wild-type controls
• gonadal fat pad mass is increased by 2.7-fold at 6 months and by 1.8-fold at 10 months of age, indicating that the differential in fat mass stabilizes with age
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growth/size/body
• although normal at 2 months of age, total body weight is significantly increased by 17% at both 6 and 10 months of age relative to wild-type controls, indicating that the weight differential stabilizes with age
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homeostasis/metabolism
• at 2 months of age, 6-hour fasting blood glucose levels are increased by 12% relative to wild-type controls
• at 6 months of age, fasted blood glucose levels are 63% higher than in wild-type controls
• by 10 months of age, fasted blood glucose levels are only 35% higher than in wild-type controls
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• homozygotes are severely hyperglycemic by 6 months of age
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• homozygotes develop insulin resistance by 10 months of age, coincident with bone marrow adipose tissue expansion
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hematopoietic system
• at 10 months of age, homozygotes show modest alterations in basal hematopoiesis, including a shift from granulopoiesis to B lymphopoiesis
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• at 10 months of age, myeloid-derived dendritic cell numbers are modestly increased in the bone marrow (+78%) and significantly increased in the spleen (+250%) relative to wild-type controls
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• at 10 months of age, B cell numbers are modestly increased in the bone marrow (+18%) relative to wild-type controls; a trend toward increased B-cells is noted in spleen
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• at 10 months of age, macrophage cell numbers are modestly increased in the bone marrow (+61%) relative to wild-type controls
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• at 10 months of age, blood monocyte numbers are significantly increased (+216%) relative to wild-type controls
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• at 10 months of age, homozygotes show a significant decrease in the number of circulating WBCs relative to wild-type controls
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• at 10 months of age, neutrophil cell numbers are modestly decreased in the bone marrow (-13%) and significantly reduced in spleen (-72%) relative to wild-type controls
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• at 10 months of age, blood B cell numbers are modestly decreased (-15%) relative to wild-type controls
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• at 10 months of age, homozygotes show a slight increase in spleen cellularity relative to wild-type controls
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immune system
• at 10 months of age, myeloid-derived dendritic cell numbers are modestly increased in the bone marrow (+78%) and significantly increased in the spleen (+250%) relative to wild-type controls
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• at 10 months of age, B cell numbers are modestly increased in the bone marrow (+18%) relative to wild-type controls; a trend toward increased B-cells is noted in spleen
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• at 10 months of age, macrophage cell numbers are modestly increased in the bone marrow (+61%) relative to wild-type controls
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• at 10 months of age, blood monocyte numbers are significantly increased (+216%) relative to wild-type controls
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• at 10 months of age, homozygotes show a significant decrease in the number of circulating WBCs relative to wild-type controls
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• at 10 months of age, neutrophil cell numbers are modestly decreased in the bone marrow (-13%) and significantly reduced in spleen (-72%) relative to wild-type controls
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• at 10 months of age, blood B cell numbers are modestly decreased (-15%) relative to wild-type controls
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• at 10 months of age, homozygotes show a slight increase in spleen cellularity relative to wild-type controls
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