Phenotypes Associated with This Genotype

Genotype
MGI:6387275

• Allelic Composition: Sqstm1^tm1Keta/Sqstm1^tm1Keta
• Genetic Background: involves: 129 * C57BL/6N

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

growth/size/body

obese ( J:264183 )

• mice develop progressive obesity

skeleton

abnormal bone structure ( J:264183 )

• mice show an age-related Pagets disease of bone-like phenotype characterized by increased bone forming (increased trabecular network and serum PINP) and bone degrading activity (increased TRAP activity and serum CTX-I)

• Pagets disease of bone-like osteolytic lesions are seen at the diaphysis area in femora of 21-month old females

• adipocyte/lipid accumulation in the bones starts between 6-9 months in females, but is not seen in males

• however, levels of pro-inflammatory cytokines are not elevated

abnormal osteoclast differentiation ( J:264183 )

• bone marrow-derived monocytes grown in culture exhibit fast and premature in vitro osteoclastogenesis

increased bone mineral density of femur ( J:264183 )

• femora maintain a relatively high bone density

increased bone volume ( J:264183 )

• bone volume fraction is higher in femora

abnormal trabecular bone morphology ( J:264183 )

• femora show elevated density of trabecular structures, especially at 9, 12, and 15 months of age

increased bone trabecula number ( J:264183 )

• increase in trabecular number in femora at 15 months of age, with differences in trabecular number starting to appear around 9 months of age

• however, trabecular thickness is not affected

decreased bone trabecular spacing ( J:264183 )

• decrease in trabecular separation in femora at 15 months of age, with differences in trabecular separation starting to appear around 9 months of age

abnormal bone remodeling ( J:264183 )

• femora maintain a relatively high bone density and thus a low trabecular separation during aging, indicating a transformation in bone turnover

• the increased trabecular bone structures and high bone-associated TRAP staining indicate increased bone turnover

abnormal osteoblast physiology ( J:264183 )

• high osteoblast activity at 21 months of age

abnormal osteoclast physiology ( J:264183 )

• high osteoclast activity at 21 months of age

cellular

abnormal osteoclast differentiation ( J:264183 )

• bone marrow-derived monocytes grown in culture exhibit fast and premature in vitro osteoclastogenesis

abnormal osteoblast physiology ( J:264183 )

• high osteoblast activity at 21 months of age

hematopoietic system

abnormal osteoclast differentiation ( J:264183 )

• bone marrow-derived monocytes grown in culture exhibit fast and premature in vitro osteoclastogenesis

abnormal osteoclast physiology ( J:264183 )

• high osteoclast activity at 21 months of age

immune system

abnormal osteoclast differentiation ( J:264183 )

• bone marrow-derived monocytes grown in culture exhibit fast and premature in vitro osteoclastogenesis

abnormal osteoclast physiology ( J:264183 )

• high osteoclast activity at 21 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Paget's disease of bone		DOID:5408	OMIM:PS167250	J:264183