Analysis Tools
mortality/aging
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• at birth, the % of surviving pups obtained from heterozygous intercrosses may not display a Mendelian distribution, depending on environmental factors
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endocrine/exocrine glands
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• adult homozygotes show a general disorganization of the thyroid follicles and flattening of the epithelium, as shown by uneven follicle sizes and reduced interstitial spaces
• however, no goiter is detected up to >18 months of age
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• in response to TSH injections, homozygotes display reduced increases of free T3 and T4 serum levels relative to wild-type mice
• notably, homozygotes exhibit a mixed hyper- and hypothyroid phenotype, dependent on the tissue studied
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• homozygotes show signs of hypothyroidism, including significantly reduced levels of free T3 T4, poor responses to TSH, increased fat content, and skeletal defects associated with a late-onset growth retardation
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• in addition to hypothyroidism, homozygotes display features of hyperthyroidism, including reduced body weight, elevated heart rate, and increased body temperature
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homeostasis/metabolism
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• both male and female homozygotes show significantly reduced free T4 levels in serum relative to wild-type littermates
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• both male and female homozygotes show significantly reduced free T3 levels in serum relative to wild-type littermates
• total T3 levels are significantly reduced only in female homozygotes
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• homozygotes display significantly reduced serum levels of IGF-I relative to wild-type mice
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• homozygotes display an increased body temperature (36.9 0.1 C) relative to wild-type mice (36.5 0.1 C)
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• at 6-20 weeks, both male and female homozygotes display inappropriately normal serum levels of TSH, suggesting an alteration in the pituitary-thyroid axis
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growth/size/body
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• both female and male homozygotes show a slightly reduced body weight from birth to adulthood relative to wild-type mice
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• both female and male homozygotes show a slightly delayed growth spurt during the first 9 weeks of life relative to wild-type mice
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skeleton
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• homozygotes display a 57% reduction in osteoclast activity relative to wild-type mice
• in contrast, serum levels of osteocalcin, a marker of bone formation, remain unaffected
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• homozygotes show a significant reduction in areal bone mineral (BM) content of the femur and L6 vertebrae relative to wild-type mice
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• homozygotes show a significant reduction in areal bone mineral (BM) density of the femur and L6 vertebrae relative to wild-type mice
• however, no delay in the mineralization of the epiphysis is observed
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• homozygotes exhibit decreased tibial cortical bone mineral content relative to wild-type mice
• however, no significant reduction in longitudinal bone growth is observed, such that tibias and femurs are of normal length
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• homozygotes exhibit decreased tibial cortical bone periosteal and endosteal circumferences, and cortical area relative to wild-type mice
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• homozygotes display decreased trabecular bone mineral density (BMD), as shown by a 24% reduction in proximal tibia
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adipose tissue
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• homozygotes exhibit a significant increase in fat content (121%) relative to wild-type mice
• however, serum levels of corticosterone and leptin are not significantly altered
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reproductive system
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• female homozygotes display a slightly prolonged estrous cycle, suggesting aberrant ovulation
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• female homozygotes generally fail to conceive
• female homozygotes display partial fertility but only under optimized animal care conditions
• homozygous intercrosses rarely generate litters
• Background Sensitivity: breeding abnormalities are exacerbated after the mutation is backcrossed for two generations onto the C57BL/6J background
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behavior/neurological
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• if pups are born, female homozygotes fail to rear their offspring
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cardiovascular system
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• homozygotes display a 10% increase in basal heart rate relative to wild-type littemates, despite their lower serum T3 levels
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immune system
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• homozygotes display a 57% reduction in osteoclast activity relative to wild-type mice
• in contrast, serum levels of osteocalcin, a marker of bone formation, remain unaffected
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hematopoietic system
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• homozygotes display a 57% reduction in osteoclast activity relative to wild-type mice
• in contrast, serum levels of osteocalcin, a marker of bone formation, remain unaffected
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