Phenotypes Associated with This Genotype

Genotype
MGI:5695740

• Allelic Composition: Ppard^tm1Dsvg/Ppard^tm1Dsvg
• Genetic Background: involves: 129S2/SvPas * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

adipose tissue

increased bone marrow adipose tissue amount ( J:219677 )

• older mice exhibit increased bone marrow adiposity in the metaphysis of the distal femur

• mesenchymal stem cells from bone marrow show increased propensity to form mature adipocytes

behavior/neurological

decreased aerobic running capacity ( J:219677 )

• maximal running distance is reduced in old mice

• however, the maximal speed is unchanged

cellular

impaired osteoblast differentiation ( J:219677 )

• marker analysis indicates altered osteoblast differentiation

• primary osteoblast cultures from calvariae show increased propensity to form mature adipocytes with lower osteoblast differentiation under adipogenic conditions

growth/size/body

decreased lean body mass ( J:219677 )

• however, body weight and lean mass is not different at 1 month of age

• between 1 and 12 months of age, total and limb lean mass gains are lower

hematopoietic system

increased osteoclast cell number ( J:219677 )

• higher osteoclast number and surface

homeostasis/metabolism

decreased aerobic running capacity ( J:219677 )

• maximal running distance is reduced in old mice

• however, the maximal speed is unchanged

abnormal circulating protein level ( J:219677 )

• increase in circulating myostatin levels

impaired glucose tolerance ( J:219677 )

• mice are glucose intolerant at 4 and 18 months of age, however glucose intolerance is maintained and not exacerbated with age

abnormal response to exercise ( J:219677 )

• mutants show diminished muscle and bone anabolic response to exercise; exercise does not increase body weight, limb lean mass or force, or femur bone mineral density and cortical structure, does not stimulate bone formation at the endocortical and periosteal surfaces, and increases the trabecular bone volume/tissue volume to a lower extent as it does in wild-type mice

immune system

increased osteoclast cell number ( J:219677 )

• higher osteoclast number and surface

muscle

decreased skeletal muscle mass ( J:219677 )

• gastrocnemius muscle mass becomes lower with age, with a 4.6% decrease at 4 months and 30.8% decrease at 18 months of age

muscle weakness ( J:219677 )

• muscle strength declines between 1 and 12 months of age

skeleton

increased bone marrow adipose tissue amount ( J:219677 )

• older mice exhibit increased bone marrow adiposity in the metaphysis of the distal femur

• mesenchymal stem cells from bone marrow show increased propensity to form mature adipocytes

impaired osteoblast differentiation ( J:219677 )

• marker analysis indicates altered osteoblast differentiation

• primary osteoblast cultures from calvariae show increased propensity to form mature adipocytes with lower osteoblast differentiation under adipogenic conditions

increased osteoclast cell number ( J:219677 )

• higher osteoclast number and surface

decreased bone mineral density ( J:219677 )

• by 12 months of age, total body and femur bone mineral densities are lower

decreased bone mineral density of femur ( J:219677 )

decreased bone volume ( J:219677 )

• decline in bone volume/tissue volume (BV/TV) ratio

abnormal compact bone morphology ( J:219677 )

• mice exhibit increased endocortical porosity at 18 months of age

abnormal compact bone volume ( J:219677 )

• mice exhibit lower cortical tissue volume and bone volume at 18 months of age

abnormal bone ossification ( J:219677 )

• bone-forming indices are lower, particularly at the periosteal surfaces at older ages and bone formation markers are lower at 18 months of age

• axial compression of the tibia increases bone marrow density and cortical tissue volume and stimulates periosteal bone formation similarly to wild-type mice, however at the endocortical surface, loading does not increase the bone-forming indices in the mutants

increased bone resorption ( J:219677 )

• bone resorption markers are higher indicating altered bone turnover

decreased bone stiffness ( J:219677 )

• in three point bending, ultimate force and stiffness are lower in 4, 12, and 18 months of age

decreased bone strength ( J:219677 )

• mice exhibit accelerated decline in bone strength with age

decreased energy dissipated prior to femur fracture ( J:219677 )

• the energy to fracture is lower at 18 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:219677