Phenotypes Associated with This Genotype

Genotype
MGI:3815037

• Allelic Composition: Ly6a^tm1Pmf/Ly6a^tm1Pmf
• Genetic Background: C.129P2-Ly6a^tm1Pmf

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

skeleton

abnormal osteoblast differentiation ( J:83409 )

• the number of ostoblast colony forming units cultured from bone marrow of 2-month old mice is half that of controls

• in vitro bone nodule formation is reduced by more than half in these bone marrow cultures

• committed osteoblast progenitors have a 7% increase in doubling time compared to controls

• the number of osteoblast progenitors isolated from bone marrow cultures is reduced

• however, the ratio of osteoblast progenitors to total number of stromal progenitors is the same

abnormal osteoclast differentiation ( J:83409 )

• osteoblast and splenic co-cultures generated less than 10% of the osteoclasts found in co-cultures of wild-type cells

• when mutant osteoblastic cells were used with wild-type splenocytes, markedly reduced numbers of wild-type osteoclasts are generated indicating a primary stromal cell defect in osteoclastogenesis

abnormal osteoblast physiology ( J:83409 )

• bone formation is essentially normal at 2 months of age but is dramatically reduced by 6 months of age

decreased osteoclast cell number ( J:83409 )

• the absolute number of osteoclasts is reduced by more than 40% in both 2- and 9- month old femurs

• osteoblast and splenic co-cultures generated less than 10% of the osteoclasts found in co-cultures of wild-type cells

decreased bone mineral content ( J:83409 )

• bone mineral content does not change between 2 months of age to 12 months of age while mineral content is increased in wild-type mice during this time period

decreased bone trabecula number ( J:83409 )

• femurs have 27% fewer trabeculae compared with control bones at 4 months of age and 58% compared with bones at 15 months of age

osteoporosis ( J:83409 )

• mice one year of age have the same bone mass density as 8 week old mice, which is significantly less than the bone mass of one year old wild-type mice

• the greatest decrease in bone mass density occurs in vertebrae

decreased osteoid volume ( J:83409 )

• the percent of osteoid in femurs are significantly lower in both 4- and 15- month old bones

decreased bone ossification ( J:83409 )

• bone formation is essentially normal at 2 months of age but is dramatically reduced by 6 months of age

decreased bone strength ( J:83409 )

• compression testing of 15-month old vertebrae shows the bone is not as stiff and is substantially weaker and more compliant than bones from wild-type animals

• the yield stress and failure stress of vertebrae are reduced by about a third while the elastic modulus is half that of controls

• femurs from 15-month-old mice have a similar stiffness to wild-type bones but are weaker and considerably more brittle

hematopoietic system

abnormal osteoclast differentiation ( J:83409 )

• osteoblast and splenic co-cultures generated less than 10% of the osteoclasts found in co-cultures of wild-type cells

• when mutant osteoblastic cells were used with wild-type splenocytes, markedly reduced numbers of wild-type osteoclasts are generated indicating a primary stromal cell defect in osteoclastogenesis

abnormal common myeloid progenitor cell morphology ( J:83409 )

• the total number of stromal progenitors found in bone marrow is reduced in 2- and 7- month old mice by 45% and 67%, respectively, compared to controls

• serial passaging of bone marrow stromal cultures reduces the number of stromal progenitors by more than half per passage, indicating a defect in self renewal

decreased osteoclast cell number ( J:83409 )

• the absolute number of osteoclasts is reduced by more than 40% in both 2- and 9- month old femurs

• osteoblast and splenic co-cultures generated less than 10% of the osteoclasts found in co-cultures of wild-type cells

adipose tissue

abnormal fat cell morphology ( J:83409 )

• bone marrow stroma contains two-thirds less adipocyte progenitors than controls

immune system

abnormal osteoclast differentiation ( J:83409 )

• osteoblast and splenic co-cultures generated less than 10% of the osteoclasts found in co-cultures of wild-type cells

• when mutant osteoblastic cells were used with wild-type splenocytes, markedly reduced numbers of wild-type osteoclasts are generated indicating a primary stromal cell defect in osteoclastogenesis

decreased osteoclast cell number ( J:83409 )

• the absolute number of osteoclasts is reduced by more than 40% in both 2- and 9- month old femurs

• osteoblast and splenic co-cultures generated less than 10% of the osteoclasts found in co-cultures of wild-type cells

cellular

abnormal osteoblast differentiation ( J:83409 )

• the number of ostoblast colony forming units cultured from bone marrow of 2-month old mice is half that of controls

• in vitro bone nodule formation is reduced by more than half in these bone marrow cultures

• committed osteoblast progenitors have a 7% increase in doubling time compared to controls

• the number of osteoblast progenitors isolated from bone marrow cultures is reduced

• however, the ratio of osteoblast progenitors to total number of stromal progenitors is the same

abnormal osteoclast differentiation ( J:83409 )

• osteoblast and splenic co-cultures generated less than 10% of the osteoclasts found in co-cultures of wild-type cells

• when mutant osteoblastic cells were used with wild-type splenocytes, markedly reduced numbers of wild-type osteoclasts are generated indicating a primary stromal cell defect in osteoclastogenesis

abnormal osteoblast physiology ( J:83409 )

• bone formation is essentially normal at 2 months of age but is dramatically reduced by 6 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteoporosis		DOID:11476	OMIM:166710	J:83409