All Phenotypes Lrp5<tm1Kry> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Lrp5^tm1Kry
targeted mutation 1, Gerard Karsenty
MGI:2183279

Summary

10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lrp5^tm1Kry/Lrp5^tm1Kry	either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6J)	MGI:3664613
hm2	Lrp5^tm1Kry/Lrp5^tm1Kry	involves: 129S1/Sv * 129X1/SvJ	MGI:3793503
ht3	Lrp5^tm1Kry/Lrp5⁺	either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6J)	MGI:3664614
ht4	Lrp5^tm1Kry/Lrp5⁺	involves: 129S1/Sv * 129X1/SvJ	MGI:3837401
cn5	Lrp5^tm1Kry/Lrp5^tm1Kry Igs1^{tm2(CAG-Bgeo,-Ndp,-EGFP)Nat}/Igs1^{tm2(CAG-Bgeo,-Ndp,-EGFP)Nat} Edil3^{Tg(Sox2-cre)1Amc}/?	involves: 129 * C57BL/6 * CBA	MGI:4412197
cn6	Creb1^tm3Gsc/Creb1⁺ Lrp5^tm1Kry/Lrp5⁺ Tg(Col1a1-cre)1Kry/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * FVB	MGI:3837412
cn7	Lrp5^tm1Kry/Lrp5^tm1Kry Tph1^tm1Kry/Tph1⁺ Tg(Vil1-cre)20Syr/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:3837415
cx8	Htr1b^tm1Rhn/Htr1b⁺ Lrp5^tm1Kry/Lrp5^tm1Kry	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:3837416
cx9	Lrp5^tm1Kry/Lrp5^tm1Kry Sostdc1^tm1Snd/Sostdc1^tm1Snd	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5770364
cx10	Lrp5^tm1Kry/Lrp5^tm1Kry Sostdc1^tm2Snd/Sostdc1^tm2Snd	involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ	MGI:5770375

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

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lrp5^tm1Kry mutation (0 available); any Lrp5 mutation (81 available)

♀	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

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

Allelic Composition	Lrp5^tm1Kry/Lrp5^tm1Kry
Genetic Background	involves: 129S1/Sv * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lrp5^tm1Kry mutation (0 available); any Lrp5 mutation (81 available)

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

vision/eye

abnormal retina vasculature morphology ( J:135279 , J:144980 )

• hyperpermeable retinal vessels (J:135279)

• reduced density of retinal small vessels and capillaries and an attenuated and abnormally patterned vasculature due to incomplete development (J:135279)

• at P7, retinal vascular density is reduced compared to in wild-type retina (J:144980)

persistence of hyaloid vascular system ( J:101493 , J:146078 )

• associated with reduced rate of entry into the cell cycle (J:101493)

• persists on both a normal chow and low tryptophan diet (J:146078)

homeostasis/metabolism

decreased serotonin level ( J:146078 )

• when fed a diet containing 75% less tryptophan than normal, circulating serotonin levels are reduced 8- to 10-fold

increased serotonin level ( J:146078 )

• circulating serotonin levels increase with age

skeleton

skeleton phenotype ( J:146078 )

N	• despite the decrease in osteoblast numbers in vivo, osteoblast proliferation ex vivo is normal

decreased bone mass ( J:146078 )

• on a normal diet bone mass is reduced

• when fed a diet containing 75% less tryptophan than normal, bone mass is normalized

abnormal bone mineralization ( J:216098 )

• variable reduction in mineralization of phalanges at P0, with incomplete penetrance

cardiovascular system

abnormal retina vasculature morphology ( J:135279 , J:144980 )

• hyperpermeable retinal vessels (J:135279)

• reduced density of retinal small vessels and capillaries and an attenuated and abnormally patterned vasculature due to incomplete development (J:135279)

• at P7, retinal vascular density is reduced compared to in wild-type retina (J:144980)

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

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lrp5^tm1Kry mutation (0 available); any Lrp5 mutation (81 available)

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

Abnormal osteogenesis in Lrp5^tm1Kry/Lrp5⁺ and Lrp5^tm1Kry/Lrp5^tm1Kry mice

skeleton

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 (88.6 um³/year vs 60.5 um³/year)

decreased bone volume ( J:75973 )

• heterozygotes have significantly decreased bone volume compared to wild-type

decreased bone mass ( J:75973 )

• less severe than in homozygotes

abnormal bone ossification ( J:75973 )

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

delayed bone ossification ( J:75973 )

• delay is milder in heterozygotes

cellular

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 (88.6 um³/year vs 60.5 um³/year)

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

Allelic Composition	Lrp5^tm1Kry/Lrp5⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lrp5^tm1Kry mutation (0 available); any Lrp5 mutation (81 available)

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

homeostasis/metabolism

increased serotonin level ( J:146078 )

• circulating serotonin levels increase with age

Allelic Composition	Lrp5^tm1Kry/Lrp5^tm1Kry Igs1^{tm2(CAG-Bgeo,-Ndp,-EGFP)Nat}/Igs1^{tm2(CAG-Bgeo,-Ndp,-EGFP)Nat} Edil3^{Tg(Sox2-cre)1Amc}/?
Genetic Background	involves: 129 * C57BL/6 * CBA

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Edil3^{Tg(Sox2-cre)1Amc} mutation (5 available); any Edil3 mutation (42 available)
Igs1^{tm2(CAG-Bgeo,-Ndp,-EGFP)Nat} mutation (1 available); any Igs1 mutation (10 available)
Lrp5^tm1Kry mutation (0 available); any Lrp5 mutation (81 available)

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

mortality/aging

embryonic lethality, incomplete penetrance ( J:154020 )

• Background Sensitivity: mid-gestational lethality but some survival improvement

growth/size/body

embryonic growth retardation ( J:154020 )

• Background Sensitivity: growth retardation moderated

cardiovascular system

abnormal descending aorta morphology ( J:154020 )

• Background Sensitivity: disruption less severe

abnormal angiogenesis ( J:154020 )

• Background Sensitivity: less severely disrupted

embryo

embryonic growth retardation ( J:154020 )

• Background Sensitivity: growth retardation moderated

Allelic Composition	Creb1^tm3Gsc/Creb1⁺ Lrp5^tm1Kry/Lrp5⁺ Tg(Col1a1-cre)1Kry/0
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * FVB

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Creb1^tm3Gsc mutation (2 available); any Creb1 mutation (59 available)
Lrp5^tm1Kry mutation (0 available); any Lrp5 mutation (81 available)
Tg(Col1a1-cre)1Kry mutation (2 available)

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

skeleton

decreased bone mass ( J:146078 )

• phenotype is indistinguishable from mice homozygous null for Lrp5

decreased bone ossification ( J:146078 )

• decreased bone formation

Allelic Composition	Lrp5^tm1Kry/Lrp5^tm1Kry Tph1^tm1Kry/Tph1⁺ Tg(Vil1-cre)20Syr/0
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lrp5^tm1Kry mutation (0 available); any Lrp5 mutation (81 available)
Tg(Vil1-cre)20Syr mutation (4 available)
Tph1^tm1Kry mutation (0 available); any Tph1 mutation (40 available)

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

skeleton

skeleton phenotype ( J:146078 )

N	• loss of expression of 1 copy of Tph1 in the gut rescues the bone phenotype seen in Lrp5 null mice

Allelic Composition	Htr1b^tm1Rhn/Htr1b⁺ Lrp5^tm1Kry/Lrp5^tm1Kry
Genetic Background	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Htr1b^tm1Rhn mutation (3 available); any Htr1b mutation (26 available)
Lrp5^tm1Kry mutation (0 available); any Lrp5 mutation (81 available)

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

skeleton

skeleton phenotype ( J:146078 )

N	• loss of expression of 1 copy of Htrb1 rescues the bone phenotype seen in Lrp5 null mice

Allelic Composition	Lrp5^tm1Kry/Lrp5^tm1Kry Sostdc1^tm1Snd/Sostdc1^tm1Snd
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lrp5^tm1Kry mutation (0 available); any Lrp5 mutation (81 available)
Sostdc1^tm1Snd mutation (0 available); any Sostdc1 mutation (28 available)

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

skeleton

skeleton phenotype ( J:216098 )

N	• at 1.5 months of age, active trabecular osteoblast numbers normalize to wild-type levels

Allelic Composition	Lrp5^tm1Kry/Lrp5^tm1Kry Sostdc1^tm2Snd/Sostdc1^tm2Snd
Genetic Background	involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lrp5^tm1Kry mutation (0 available); any Lrp5 mutation (81 available)
Sostdc1^tm2Snd mutation (0 available); any Sostdc1 mutation (28 available)

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

Genetic correction of Wise with Lrp5 during ossification

skeleton

skeleton phenotype ( J:216098 )

N	• at PO, mineralization of phalanges is restored to near wild-type levels or those seen in single Lrp5^tm1Kry homozygotes; clearly seen in hindlimb digits 4 and 5

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