Phenotypes Associated with This Genotype

Genotype
MGI:3829994

• Allelic Composition: Ncor2^tm1Rev/Ncor2^tm1Rev
• Genetic Background: involves: 129/Sv * C57BL/6

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

Defective bone growth in Ncor2^tm1Rev/Ncor2^tm1Rev mice

homeostasis/metabolism

increased circulating glucose level ( J:142665 )

abnormal circulating hormone level ( J:202976 )

• increase in circulating thrombopoietin levels

abnormal circulating enzyme level ( J:202976 )

• serum concentrations of the osteoclast-specific tartrate-resistant acid phosphatase are increased

decreased body temperature ( J:142665 )

• when resting or active

decreased energy expenditure ( J:142665 )

• mice expend 20% less energy than wild-type mice

abnormal gas homeostasis ( J:142665 )

• respiratory rates are decreased compared to in wild-type mice

• the respiratory exchange ratio is reduced compared to in wild-type mice

decreased carbon dioxide production ( J:142665 )

decreased oxygen consumption ( J:142665 )

abnormal gluconeogenesis ( J:142665 )

• baseline hepatic glucose production is higher than in wild-type mice

insulin resistance ( J:142665 )

• insulin-stimulated glucose disposal is diminished compared to in wild-type mice

increased adiponectin level ( J:142665 )

abnormal metabolism ( J:142665 )

• mice exhibit decreased metabolic rates compared to in wild-type mice

abnormal physiological response to xenobiotic ( J:142665 )

• mice treated with propylthiouracil/methimazole to render them hypothyroid exhibit decreased hypercholesterolemia compared to similarly treated wild-type mice

adipose tissue

adipose tissue phenotype ( J:142665 )

N • despite increased fat content, adipocyte size is normal

increased epididymal fat pad weight ( J:142665 )

• when fed a standard or high fat diet, epididymal fat pad to body weight ratio is increased 70% compared to in wild-type mice

increased percent body fat/body weight ( J:142665 )

• when fed a standard or high fat diet

growth/size/body

decreased body weight ( J:142665 )

• mice are 10% lighter than wild-type mice

enlarged spleen ( J:202976 )

• by 8 months of age, mice show splenomegaly

cellular

abnormal cell differentiation ( J:142665 )

• 100% of mouse embryonic fibroblasts (MEFs) can be induced to differentiate into adipose cells compared to 5% of wild-type cells

• some MEFs undergone spontaneous differentiation into adipose cells unlike wild-type cells

cardiovascular system

thin ventricular wall ( J:142665 )

• at birth mice exhibit a thin ventricular wall compared to in wild-type mice

• however, by adulthood hearts morphology is normal

nervous system

nervous system phenotype ( J:142665 )

N • unlike mice homozygous for a null allele, brain development is normal

behavior/neurological

hindlimb paresis ( J:202976 )

• hind limb paresis by 8 months of age

hematopoietic system

extramedullary hematopoiesis ( J:202976 )

• extramedullary hematopoiesis is evident in the enlarged spleen

abnormal bone marrow cell number ( J:202976 )

• decrease in hematopoietic progenitors in the bone marrow

• increase in nonhematopoietic cells in the bone marrow, with much of the marrow cavity occupied by reticular cells and collagen fibers

increased megakaryocyte cell number ( J:202976 )

increased erythroid progenitor cell number ( J:202976 )

increased osteoclast cell number ( J:202976 )

• about 25% increase in overall osteoclast numbers, however osteoblast activity is not affected

• increase in osteoclast numbers along the endosteal surface

abnormal hematopoietic stem cell morphology ( J:202976 )

• increase in splenic hematopoietic progenitors with a concurrent decrease of hematopoietic progenitors in the bone marrow

abnormal spleen morphology ( J:202976 )

• increase in splenic hematopoietic progenitors

enlarged spleen ( J:202976 )

• by 8 months of age, mice show splenomegaly

immune system

increased osteoclast cell number ( J:202976 )

• about 25% increase in overall osteoclast numbers, however osteoblast activity is not affected

• increase in osteoclast numbers along the endosteal surface

abnormal spleen morphology ( J:202976 )

• increase in splenic hematopoietic progenitors

enlarged spleen ( J:202976 )

• by 8 months of age, mice show splenomegaly

skeleton

increased osteoclast cell number ( J:202976 )

• about 25% increase in overall osteoclast numbers, however osteoblast activity is not affected

• increase in osteoclast numbers along the endosteal surface

abnormal bone marrow cavity morphology ( J:202976 )

• bone marrow cavities from 8 month old mice contain large amounts of small spicules and increased numbers of CD34+ microvessels

abnormal bone marrow morphology ( J:202976 )

• 100% increase in levels of thrombopoietin in the bone marrow

myelofibrosis ( J:202976 )

• seen by 8 months of age

decreased compact bone thickness ( J:202976 )

• cortical thinning without significant differences in cortical bone density

abnormal trabecular bone morphology ( J:202976 )

• increase in bone volume in trabecular regions, with a decrease in trabecular bone spacing and increase in trabecular bone numbers

increased trabecular bone volume ( J:202976 )

increased bone trabecula number ( J:202976 )

osteosclerosis ( J:202976 )

• seen by 8 months of age

abnormal skeleton physiology ( J:202976 )

• reduction in radial growth without any significant differences in length

decreased bone strength ( J:202976 )

• about 20% reduction in fracture load when mice are subjected to a femoral neck fracture assay

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myelofibrosis		DOID:4971	OMIM:254450	J:202976