Phenotypes associated with this allele

• Allele Symbol: Esrra^tm1Vgi
• Allele Name: targeted mutation 1, Vincent Giguere
• Allele ID: MGI:2682818
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Esrra^tm1Vgi/Esrra^tm1Vgi	involves: 129S1/Sv * 129X1/SvJ	MGI:4461916
hm2	Esrra^tm1Vgi/Esrra^tm1Vgi	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:2682828
hm3	Esrra^tm1Vgi/Esrra^tm1Vgi	involves: C57BL/6	MGI:2682830

Genotype
MGI:4461916

hm1

• Allelic Composition: Esrra^tm1Vgi/Esrra^tm1Vgi
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

skeleton

abnormal bone structure ( J:160910 )

• 79% increase in bone surface of the tibia

abnormal osteoclast differentiation ( J:160910 )

• RANKL-mediated and rosiglitazone-stimulated osteoclast differentiation is impaired compared with similarly treated wild-type cells

decreased osteoclast cell number ( J:160910 )

• osteoclast surface and osteoclast numbers are decreased compared to in wild-type mice

increased osteoblast cell number ( J:160910 )

• osteoblast surface and osteoclast numbers are increased compared to in wild-type mice

abnormal trabecular bone morphology ( J:160910 )

• mice exhibit an increase in trabecular bone volume to tissue volume ration, bone surface, trabecular number and connectivity density but a decrease in trabecular separation and structure model index compared with wild-type mice

increased trabecular bone volume ( J:160910 )

• in the tibia

osteopetrosis ( J:160910 )

decreased bone resorption ( J:160910 )

• rosiglitazone-induced bone resorption and bone loss is reduced compared to in wild-type mice

immune system

abnormal osteoclast differentiation ( J:160910 )

• RANKL-mediated and rosiglitazone-stimulated osteoclast differentiation is impaired compared with similarly treated wild-type cells

decreased osteoclast cell number ( J:160910 )

• osteoclast surface and osteoclast numbers are decreased compared to in wild-type mice

increased splenocyte number ( J:160910 )

hematopoietic system

abnormal osteoclast differentiation ( J:160910 )

• RANKL-mediated and rosiglitazone-stimulated osteoclast differentiation is impaired compared with similarly treated wild-type cells

extramedullary hematopoiesis ( J:160910 )

• in the spleen

decreased bone marrow cell number ( J:160910 )

decreased osteoclast cell number ( J:160910 )

• osteoclast surface and osteoclast numbers are decreased compared to in wild-type mice

increased splenocyte number ( J:160910 )

cellular

abnormal osteoclast differentiation ( J:160910 )

• RANKL-mediated and rosiglitazone-stimulated osteoclast differentiation is impaired compared with similarly treated wild-type cells

Genotype
MGI:2682828

hm2

• Allelic Composition: Esrra^tm1Vgi/Esrra^tm1Vgi
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

adipose tissue

increased brown fat cell lipid droplet size ( J:119525 )

decreased fat cell mitochondrial DNA content ( J:119525 )

• in brown adipocytes

decreased white fat cell size ( J:86433 )

• homozygotes display an apparently normal adipocyte number with reduced adipocyte size in epididymal white adipose tissue (WAT)

decreased epididymal fat pad weight ( J:86433 )

• at 26 weeks of age, homozygotes display a 50% to 60% reduction in epididymal fat pad weight relative to wild-type and heterozygous littermates

decreased inguinal fat pad weight ( J:86433 )

• at 26 weeks of age, homozygotes display a 50% to 60% reduction in inguinal fat pad weight relative to wild-type and heterozygous littermates

decreased retroperitoneal fat pad weight ( J:86433 )

• at 26 weeks of age, homozygotes display a 50% to 60% reduction in peritoneal fat pad weight relative to wild-type and heterozygous littermates

decreased percent body fat/body weight ( J:86433 )

• homozygotes display a reduced total fat mass % (80.6%) relative to wild-type littermates

abnormal adipose tissue physiology ( J:86433 )

• DNA microarray analysis of gene expression in adipose tissue shows altered regulation of several enzymes involved in lipid, eicosanoid, and steroid synthesis, as well as changes in the expression of genes regulating adipogenesis and energy metabolism

• in most cases, changes in gene expression noted in brown fat are similar to those observed in white fat

cellular

decreased fat cell mitochondrial DNA content ( J:119525 )

• in brown adipocytes

decreased mitochondrial number ( J:119525 )

• in brown adipocytes

abnormal cellular respiration ( J:119525 )

• reduced respiratory capacity in brown adipocytes with an intrinsic decreased oxidative capacity

growth/size/body

increased percent water in carcass ( J:86433 )

• homozygotes display a compensatory increase in water content % (106.4%) relative to wild-type littermates

increased lean body mass ( J:86433 )

• homozygotes display a compensatory increase in lean body mass % (105%) relative to wild-type littermates

decreased body weight ( J:86433 )

• starting at 2 weeks of age, homozygotes show a significant decrease in mean body weight relative to wild-type littermates

• at 10 weeks of age, both male and female homozygotes display ~85% of wild-type body weight

• however, the body length (nose to anus) of male and female homozygotes is not significantly altered at 10 weeks of age

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:86433 )

N • homozygotes exhibit normal food consumption and energy expenditure, with no significant differences in fasting glucose levels, in serum free fatty acids, or in triglyceride levels relative to wild-type littermates

impaired adaptive thermogenesis ( J:119525 )

abnormal lipid homeostasis ( J:86433 )

• after i.p. injection of ³H₂O, homozygotes incorporate 30% to 55% less ³H into adipose tissue lipids relative to wild-type littermates, indicating a significant decrease in lipogenesis

increased triglyceride level ( J:119525 )

• 2.5-fold in brown adipocytes

Genotype
MGI:2682830

hm3

• Allelic Composition: Esrra^tm1Vgi/Esrra^tm1Vgi
• Genetic Background: involves: C57BL/6

growth/size/body

decreased susceptibility to diet-induced obesity ( J:86433 )

• when 10-wk-old homozygotes are fed a high-fat diet for 5 weeks, they exhibit a significant reduction in weight gain % in the third week of feeding, and weigh only slightly more than wild-type mice fed a normal diet at the end of 5 weeks

homeostasis/metabolism

decreased susceptibility to diet-induced obesity ( J:86433 )

• when 10-wk-old homozygotes are fed a high-fat diet for 5 weeks, they exhibit a significant reduction in weight gain % in the third week of feeding, and weigh only slightly more than wild-type mice fed a normal diet at the end of 5 weeks