Phenotypes Associated with This Genotype

Genotype
MGI:3664613

• Allelic Composition: Lrp5^tm1Kry/Lrp5^tm1Kry
• Genetic Background: either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6J)

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

Low bone mass in Lrp5^tm1Kry/Lrp5^tm1Kry mice

mortality/aging

postnatal lethality, incomplete penetrance ( J:75973 )

• a small but significant number of mutants die within the first month, likely as a result of bone fractures

skeleton

skeleton phenotype ( J:75973 )

N • some homozygotes walk with noticeable limps, observed at 2 months of age, resulting from tibial fractures

abnormal osteoblast physiology ( J:75973 )

• in 6-month-old mice, a 2-fold decrease in bone formation rate (BFR) is observed; similar results are seen in 2- and 4-month-old animals

• this is due to decreased matrix apposition rate (MAR - amount of bone matrix deposited per osteoblast cluster; 0.75 um/day vs 0.45 um/day in wild-type); similar results are seen in 2- and 4-month-old animals

decreased bone volume ( J:75973 )

• there is decreased bone volume compared to wild-type

decreased osteoblast cell number ( J:75973 )

• mutant have significantly decreased numbers in the primary and secondary spongiosa

• in calvaria, osteoblasts are reduced in number and show lower levels of proliferation (lower mitotic index)

abnormal trabecular bone morphology ( J:75973 )

• at 2 weeks of age, mice show decreased mineralized bone in the primary spongiosa

decreased bone mass ( J:75973 )

• all homozygotes have a low bone mass phenotype at 2 months of age in all animals regardless of sex and at all stages analyzed

• bone mass remains lower in mutants throughout life

abnormal bone ossification ( J:75973 )

• bone formation is abnormal, but bone resorption does not appear to be affected

delayed bone ossification ( J:75973 )

• at E17.5 no defect in ossification is observed, but a subtle delay is seen in the digits of newborn mutants; fifth middle phalangeal ossification center is absent

• in 4-day old mutants delay is more pronounced, with absent or reduced ossification centers of the wrist, distal metacarpal bones, femora, humeri and ulnae

vision/eye

abnormal eye development ( J:75973 )

persistence of hyaloid vascular system ( J:75973 )

• in 70% of 6-month old mutants hyaloid vessels are present in the eyes; regression of capillary networks is delayed in mutants analyzed between P3-P8 compared to wild-type and heterozygotes

cellular

decreased apoptosis ( J:75973 )

• mutants show lower levels of macrophage-mediated apoptosis in hyaloid vessel segments of the eye at all time points, compared to wild-type

abnormal osteoblast physiology ( J:75973 )

• in 6-month-old mice, a 2-fold decrease in bone formation rate (BFR) is observed; similar results are seen in 2- and 4-month-old animals

• this is due to decreased matrix apposition rate (MAR - amount of bone matrix deposited per osteoblast cluster; 0.75 um/day vs 0.45 um/day in wild-type); similar results are seen in 2- and 4-month-old animals

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteoporosis-pseudoglioma syndrome		DOID:0060849	OMIM:259770	J:75973