Phenotypes Associated with This Genotype

Genotype
MGI:5803721

• Allelic Composition: Notch2^tm1.1Ecan/Notch2⁺
• Genetic Background: involves: 129 * 129S1/Sv * C57BL/6J

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

growth/size/body

decreased body weight ( J:230045 )

• mice weight about 20% less than controls at 1 month of age, however as mice mature, they weight about 10% less at 3 months of age

skeleton

abnormal osteoclast morphology ( J:230045 )

• 25% increase in the fraction of B220^-CD3^-CD11b^-/lo, CD115 (c-Fms)^high CD117 (c-Kit)^high cells in the bone marrow, indicating an increase in the pre-osteoclast cell pool

abnormal osteoclast differentiation ( J:230045 )

• osteoclast differentiation and bone resorption in response to receptor activator of nuclear factor kappaB ligand in vitro are increased

increased osteoclast cell number ( J:230045 )

• increase in endocortical osteoclast number and eroded surface in 1 month old mice, however this increase is no longer significant at 3 months of age

• however, no change in osteoblast number/perimeter, osteoblast surface, bone formation rate, or osteocyte number/bone area, indicating enhanced bone resorption without a coupled bone-forming response

• osteoblast, osteoclast, and osteocyte numbers are normal in 3 month old mice

short femur ( J:230045 )

• femoral length is 12% shorter at 1 month of age, but at 3 months of age, femoral length in males is no different from controls and is only 5% shorter in females

decreased bone mineral density ( J:230045 )

• osteopenia affecting both cancellous and cortical bone

• osteopenia is less pronounced in females than males at 1 month of age but as females mature, osteopenia becomes more evident

decreased bone volume ( J:230045 )

• decrease in bone volume/tissue volume is secondary to a decrease in trabecular number

decreased trabecular bone volume ( J:230045 )

• 50% and 20% decrease in trabecular bone volume at 1 month of age in males and females, respectively

• non-significant decrease in cancellous bone volume of 30% in males and a significant decrease of 50% in females at 3 months of age

abnormal compact bone morphology ( J:230045 )

• cortical bone is porous

• decrease in cortical bone and overall bone size is more pronounced at 1 month of age than 3 months of age, although cortical bone architecture remains affected at 3 months

decreased compact bone area ( J:230045 )

decreased compact bone thickness ( J:230045 )

increased osteoblast cell number ( J:230045 )

♂ • at 3 months of age, osteoblast numbers and mineral apposition rates are increased in males, but not females

decreased bone trabecula number ( J:230045 )

decreased trabecular bone connectivity density ( J:230045 )

♂ • decrease in cancellous bone volume in males is associated with decreased connectivity

decreased trabecular bone thickness ( J:230045 )

increased bone mineralization ( J:230045 )

• at 3 months of age, osteoblast numbers and mineral apposition rates are increased in males, but not females

increased bone resorption ( J:230045 )

• enhanced bone resorption without a coupled bone-forming response at 1 month of age

hematopoietic system

abnormal osteoclast morphology ( J:230045 )

• 25% increase in the fraction of B220^-CD3^-CD11b^-/lo, CD115 (c-Fms)^high CD117 (c-Kit)^high cells in the bone marrow, indicating an increase in the pre-osteoclast cell pool

abnormal osteoclast differentiation ( J:230045 )

• osteoclast differentiation and bone resorption in response to receptor activator of nuclear factor kappaB ligand in vitro are increased

increased osteoclast cell number ( J:230045 )

• increase in endocortical osteoclast number and eroded surface in 1 month old mice, however this increase is no longer significant at 3 months of age

• however, no change in osteoblast number/perimeter, osteoblast surface, bone formation rate, or osteocyte number/bone area, indicating enhanced bone resorption without a coupled bone-forming response

• osteoblast, osteoclast, and osteocyte numbers are normal in 3 month old mice

immune system

abnormal osteoclast morphology ( J:230045 )

• 25% increase in the fraction of B220^-CD3^-CD11b^-/lo, CD115 (c-Fms)^high CD117 (c-Kit)^high cells in the bone marrow, indicating an increase in the pre-osteoclast cell pool

abnormal osteoclast differentiation ( J:230045 )

• osteoclast differentiation and bone resorption in response to receptor activator of nuclear factor kappaB ligand in vitro are increased

increased osteoclast cell number ( J:230045 )

• increase in endocortical osteoclast number and eroded surface in 1 month old mice, however this increase is no longer significant at 3 months of age

• however, no change in osteoblast number/perimeter, osteoblast surface, bone formation rate, or osteocyte number/bone area, indicating enhanced bone resorption without a coupled bone-forming response

• osteoblast, osteoclast, and osteocyte numbers are normal in 3 month old mice

limbs/digits/tail

short femur ( J:230045 )

• femoral length is 12% shorter at 1 month of age, but at 3 months of age, femoral length in males is no different from controls and is only 5% shorter in females

cellular

abnormal osteoclast differentiation ( J:230045 )

• osteoclast differentiation and bone resorption in response to receptor activator of nuclear factor kappaB ligand in vitro are increased

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Hajdu-Cheney syndrome		DOID:2736	OMIM:102500	J:230045