Phenotypes Associated with This Genotype

Genotype
MGI:5568131

• Allelic Composition: Lrrk1^tm1.1Smo/Lrrk1^tm1.1Smo
• Genetic Background: involves: 129S/Sv

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

skeleton

skeleton phenotype ( J:208677 )

N • mice do not exhibit bone loss

increased osteoclast cell number ( J:208677 )

• TRAP+

abnormal osteoclast physiology ( J:208677 )

• defective bone resorptive activity in osteoclasts

• osteoclasts fail to form peripheral sealing zone and ruffled border on bone slices

• however, osteoclast function is rescued by Y527F Src overexpression

abnormal long bone morphology ( J:208677 )

• wide long bone metaphysis and reduced long bone marrow cavity area but normal diaphysis

short femur ( J:208677 )

short tibia ( J:208677 )

abnormal long bone metaphysis morphology ( J:208677 )

• reduced mineral apposition rate and bone formation rate/bone surface

abnormal bone marrow cavity morphology ( J:208677 )

• reduced long bone marrow cavity area

increased bone mineral density ( J:208677 )

• total body and volumetric at 6 weeks

• at 70 weeks

• cortical bone hypermineralization indicated by elevated material bone mineral density values

increased compact bone thickness ( J:208677 )

• at 8 and 79 weeks

decreased susceptibility to osteoporosis ( J:208677 )

• mice are resistant to ovariectomy-induced bone loss

abnormal trabecular bone morphology ( J:208677 )

• decreased trabecular separation

• reduced trabecular bone density at 79 weeks

increased trabecular bone volume ( J:208677 )

increased bone trabecula number ( J:208677 )

increased trabecular bone thickness ( J:208677 )

osteopetrosis ( J:208677 )

• severe

osteosclerosis ( J:208677 )

• mild in the periodontal bone, nasal septum and bridge of the nose

abnormal bone mineralization ( J:208677 )

• reduced mineral apposition rate and bone formation rate/bone surface

decreased bone resorption ( J:208677 )

• reduced endocortical resorption

• extensive unresorbed cartilage below the growth plate of the distal femur and proximal tibia

• defective bone resorptive activity in osteoclasts

limbs/digits/tail

short femur ( J:208677 )

short tibia ( J:208677 )

craniofacial

craniofacial phenotype ( J:208677 )

N • mice exhibit normal incisors, molars and periodontal ligaments

abnormal facial morphology ( J:208677 )

• mild osteosclerosis in the periodontal bone, nasal septum and bridge of the nose

• however, there are no soft tissue abnormalities

growth/size/body

abnormal facial morphology ( J:208677 )

• mild osteosclerosis in the periodontal bone, nasal septum and bridge of the nose

• however, there are no soft tissue abnormalities

decreased body height ( J:208677 )

• slightly

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:208677 )

N • mice exhibit normal anabolic response

decreased circulating alkaline phosphatase level ( J:208677 )

• at 8 weeks

hematopoietic system

increased osteoclast cell number ( J:208677 )

• TRAP+

abnormal osteoclast physiology ( J:208677 )

• defective bone resorptive activity in osteoclasts

• osteoclasts fail to form peripheral sealing zone and ruffled border on bone slices

• however, osteoclast function is rescued by Y527F Src overexpression

immune system

increased osteoclast cell number ( J:208677 )

• TRAP+

abnormal osteoclast physiology ( J:208677 )

• defective bone resorptive activity in osteoclasts

• osteoclasts fail to form peripheral sealing zone and ruffled border on bone slices

• however, osteoclast function is rescued by Y527F Src overexpression

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteopetrosis		DOID:13533	OMIM:PS259700 OMIM:PS607634	J:208677