Phenotypes Associated with This Genotype

Genotype
MGI:5056475

• Allelic Composition: Sqstm1^tm1.1Sral/Sqstm1^tm1.1Sral
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * C57BL/6

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

skeleton

abnormal bone structure ( J:173755 )

• at 8 months, 7 of 10 mice exhibit focal osteolytic lesion mainly in the hind limb unlike wild-type mice

• at 12 months, 20 of 21 mice exhibit focal osteolytic lesion mainly in the hind limb unlike wild-type mice

• however, young mice exhibit normal trabecular bone density and structure

abnormal osteoclast morphology ( J:173755 )

• 3 of 20 osteoclasts from bone lesions exhibit nuclear inclusions unlike wild-type cells

• osteoclasts that differentiate from bone marrow macrophage are larger and contained more nuclei than osteoclasts that differentiate from wild-type macrophage

abnormal osteoclast differentiation ( J:173755 )

• osteoclast formation from bone marrow macrophages is increased compared to from wild-type bone marrow

increased osteoclast cell number ( J:173755 )

• within bone lesions

abnormal compact bone morphology ( J:173755 )

• within bone lesions

abnormal trabecular bone morphology ( J:173755 )

• within bone lesions

abnormal bone ossification ( J:173755 )

• mice exhibit increased bone formation 10-fold within bone lesions compared with wild-type mice

abnormal bone mineralization ( J:173755 )

• mice exhibit increased mineral apposition rate and mineralizing surface within bone lesions compared with wild-type mice

immune system

abnormal osteoclast morphology ( J:173755 )

• 3 of 20 osteoclasts from bone lesions exhibit nuclear inclusions unlike wild-type cells

• osteoclasts that differentiate from bone marrow macrophage are larger and contained more nuclei than osteoclasts that differentiate from wild-type macrophage

abnormal osteoclast differentiation ( J:173755 )

• osteoclast formation from bone marrow macrophages is increased compared to from wild-type bone marrow

increased osteoclast cell number ( J:173755 )

• within bone lesions

hematopoietic system

abnormal osteoclast morphology ( J:173755 )

• 3 of 20 osteoclasts from bone lesions exhibit nuclear inclusions unlike wild-type cells

• osteoclasts that differentiate from bone marrow macrophage are larger and contained more nuclei than osteoclasts that differentiate from wild-type macrophage

abnormal osteoclast differentiation ( J:173755 )

• osteoclast formation from bone marrow macrophages is increased compared to from wild-type bone marrow

increased osteoclast cell number ( J:173755 )

• within bone lesions

cellular

abnormal osteoclast differentiation ( J:173755 )

• osteoclast formation from bone marrow macrophages is increased compared to from wild-type bone marrow

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Paget's disease of bone		DOID:5408	OMIM:PS167250	J:173755