Phenotypes associated with this allele

• Allele Symbol: Ppard^tm1Dsvg
• Allele Name: targeted mutation 1, Beatrice Desvergne
• Allele ID: MGI:3623147
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ppard^tm1Dsvg/Ppard^tm1Dsvg	involves: 129S2/SvPas	MGI:3625364
hm2	Ppard^tm1Dsvg/Ppard^tm1Dsvg	involves: 129S2/SvPas * C57BL/6	MGI:5695740

Genotype
MGI:3625364

hm1

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

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

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:107381 )

• most homozygous mutant embryos are dead by E14.5 by heterozygous mating

• at E9.5 close to normal Mendelian ratio of homozygous mutant are alive by heterozygous mating

• small number (approximately 1.6%) of homozygous mutant embryo survive to birth

• rare live homozygous mutants breeding cause about 70% penetrance of embryonic lethal phenotype

growth/size/body

embryonic growth retardation ( J:107381 )

• E9.5 live homozygous mutant embryos presented various degrees of developmental retardation with severe growth retardation

• in most cases no gross abnormalities are found in live E9.5 mutant embryos

postnatal growth retardation ( J:107381 )

• rare live homozygous mutants exhibited initial postnatal growth retardation

• the initial growth retardation was overcome by the time the animals reached adulthood

reproductive system

reduced fertility ( J:107381 )

• among rare live homozygous mutant, both male and female mutants were subfertile

• the number of nonproductive breeding pairs were elevated in live homozygous mutants

embryo

embryonic growth retardation ( J:107381 )

• E9.5 live homozygous mutant embryos presented various degrees of developmental retardation with severe growth retardation

• in most cases no gross abnormalities are found in live E9.5 mutant embryos

abnormal placenta development ( J:107381 )

• the placentas of homozygous mutant embryos were reduced in size and very compact at E9.5

• the three layers the of placenta were altered

• the severe reduction of the giant cell layer was observed

Genotype
MGI:5695740

hm2

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

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 )

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

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

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