Phenotypes Associated with This Genotype

Genotype
MGI:6766538

• Allelic Composition: Notch2^tm1.1Hhtg/Notch2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

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

skeleton

abnormal skeleton morphology ( J:311038 )

• length of several bones, such as the L4 vertebral body and femur, are moderately, yet significantly decreased

abnormal osteoclast differentiation ( J:311038 )

• mice show elevated osteoclastogenesis

increased osteoclast cell number ( J:311038 )

• mutant calvarial osteoblasts induce a higher number of osteoclasts in wild-type bone marrow cells when grown in co-culture

decreased femur compact bone thickness ( J:311038 )

• femurs show decreased cortical thickness at 52 weeks of age

decreased diameter of femur ( J:311038 )

• femurs show decreased midshaft diameter at 12, 12, and 52 weeks of age

short femur ( J:311038 )

• length of femurs is moderately, yet significantly, decreased at 12, 24, and 52 weeks of age

short tibia ( J:311038 )

• length of tibia is moderately decreased in 24-week-old mice, but not at 12 or 52 weeks of age

short vertebral body ( J:311038 )

• length of the L4 vertebral body is moderately yet significantly decreased

decreased bone mineral density ( J:311038 )

• mice exhibit osteopenia

decreased trabecular bone volume ( J:311038 )

• femurs show decreased trabecular bone volume at 12, 12, and 52 weeks of age

• vertebral bodies L3 and L4 show a decrease of trabecular bone volume in all age groups, caused by a combination of trabecular thinning and reduced trabecular number

increased osteoblast cell number ( J:311038 )

• mice exhibit increased osteoblast number at 24 and 52 weeks of age, whereas the osteocyte population is unaffected

• mice treated with alendronate starting at 18 weeks of age until 24 weeks of age show a lower number of osteoblasts

decreased bone trabecula number ( J:311038 )

• vertebral bodies L3 and L4 show reduced trabecular number

decreased trabecular bone thickness ( J:311038 )

• vertebral bodies L3 and L4 show trabecular thinning

increased bone ossification ( J:311038 )

• bone formation rate is higher at all ages analyzed, indicating a high turnover state

• mice treated with alendronate starting at 18 weeks of age until 24 weeks of age show a lower number of osteoblasts and reduced bone formation rate indicating normalized bone formation

increased bone resorption ( J:311038 )

• increase of calvarial porosity at all ages, indicating excessive bone resorption

growth/size/body

abnormal body composition ( J:311038 )

• body mass of 24- and 52-week-old mice is reduced

cellular

abnormal osteoclast differentiation ( J:311038 )

• mice show elevated osteoclastogenesis

hematopoietic system

abnormal osteoclast differentiation ( J:311038 )

• mice show elevated osteoclastogenesis

increased osteoclast cell number ( J:311038 )

• mutant calvarial osteoblasts induce a higher number of osteoclasts in wild-type bone marrow cells when grown in co-culture

homeostasis/metabolism

increased circulating type I collagen C-terminal telopeptide level ( J:311038 )

• increase in serum beta-c-terminal telopeptide in 52-week-old mice

abnormal interleukin level ( J:311038 )

• bone marrow contains an increase in IL-6 positive cells in 24-week-old mice

increased circulating interleukin-6 level ( J:311038 )

• IL-6 levels are increased in the serum of 24-week-old mice

immune system

abnormal osteoclast differentiation ( J:311038 )

• mice show elevated osteoclastogenesis

increased osteoclast cell number ( J:311038 )

• mutant calvarial osteoblasts induce a higher number of osteoclasts in wild-type bone marrow cells when grown in co-culture

abnormal interleukin level ( J:311038 )

• bone marrow contains an increase in IL-6 positive cells in 24-week-old mice

increased circulating interleukin-6 level ( J:311038 )

• IL-6 levels are increased in the serum of 24-week-old mice

increased interleukin-6 secretion ( J:311038 )

• IL-6 levels are increased in medium conditioned by bone marrow cells treated with vitamin D3 and dexamethasone

limbs/digits/tail

decreased femur compact bone thickness ( J:311038 )

• femurs show decreased cortical thickness at 52 weeks of age

decreased diameter of femur ( J:311038 )

• femurs show decreased midshaft diameter at 12, 12, and 52 weeks of age

short femur ( J:311038 )

• length of femurs is moderately, yet significantly, decreased at 12, 24, and 52 weeks of age

short tibia ( J:311038 )

• length of tibia is moderately decreased in 24-week-old mice, but not at 12 or 52 weeks of age

renal/urinary system

renal/urinary system phenotype ( J:311038 )

N • renal cysts are not seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Hajdu-Cheney syndrome		DOID:2736	OMIM:102500	J:311038