Phenotypes associated with this allele

• Allele Symbol: Lrp4^tm1.1Pg
• Allele Name: targeted mutation 1.1, PolyGene AG
• Allele ID: MGI:6343233
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lrp4^tm1.1Pg/Lrp4^tm1.1Pg	involves: C57BL/6N	MGI:6404118
ht2	Lrp4^tm1.1Pg/Lrp4^+	involves: C57BL/6N	MGI:6404125

Genotype
MGI:6404118

hm1

• Allelic Composition: Lrp4^tm1.1Pg/Lrp4^tm1.1Pg
• Genetic Background: involves: C57BL/6N

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

skeleton

skeleton phenotype ( J:277372 )

♂N • no major skeletal abnormalities are seen in males at 5 months of age, with no bone syndactyly

thick neurocranium ( J:277372 )

♂ • skull shows increased calvarial thickness

increased femur compact bone thickness ( J:277372 )

♂ • femurs show increase in cortical thickness

♂ • however, femurs show no difference in cortical porosity or in cortical bone mineral density

increased diameter of femur ( J:277372 )

♂ • increase in femoral midshaft diameter

increased trabecular bone volume ( J:277372 )

♂ • femurs and vertebral bodies show an increase in trabecular bone volume/tissue volume

abnormal osteocyte morphology ( J:277372 )

♂ • only 0.9% of osteocytes are sclerostin-positive compared to 30.1% of osteocytes in the trabeculae of the tibia of wild-type mice

increased bone trabecula number ( J:277372 )

♂ • vertebral bodies show an increase in trabecular number

decreased bone trabecular spacing ( J:277372 )

♂ • vertebral bodies show a decrease in trabecular separation

increased trabecular bone connectivity density ( J:277372 )

♂ • femurs show an increase in trabecular connectivity density

increased trabecular bone thickness ( J:277372 )

♂ • femurs and vertebral bodies show an increase in trabecular thickness

♂ • however, no difference in trabecular bone mineral density, trabecular number or separation of the femur is seen

increased bone ossification ( J:277372 )

♂ • vertebral bodies show an increase in bone formation rate, composed of increased mineral apposition rate

♂ • vertebral bodies show an increase in the osteoblast surface per bone surface, indicating an increase in bone formation by osteoblasts

♂ • however, no significant changes in bone formation and resorption makers in the serum

increased bone strength ( J:277372 )

♂ • the force and the work or energy needed to fracture bones and the elastic modulus in a three-point bending analysis are increased, indicating increased bone strength

craniofacial

thick neurocranium ( J:277372 )

♂ • skull shows increased calvarial thickness

homeostasis/metabolism

abnormal blood homeostasis ( J:277372 )

♂ • mice show increased levels of sclerostin in the blood

limbs/digits/tail

increased femur compact bone thickness ( J:277372 )

♂ • femurs show increase in cortical thickness

♂ • however, femurs show no difference in cortical porosity or in cortical bone mineral density

increased diameter of femur ( J:277372 )

♂ • increase in femoral midshaft diameter

muscle

muscle phenotype ( J:277372 )

♂N • mice show no signs of facial distortion or muscle paralysis

renal/urinary system

renal/urinary system phenotype ( J:277372 )

♂N • kidneys appear normal and serum creatinine levels are normal, indicating normal renal function

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
sclerosteosis 2		DOID:0060757	OMIM:614305	J:277372

Genotype
MGI:6404125

ht2

• Allelic Composition: Lrp4^tm1.1Pg/Lrp4⁺
• Genetic Background: involves: C57BL/6N

skeleton

increased bone strength ( J:277372 )

♂ • mice show an increase in the work needed to fracture the femur and an increase in the work needed to reach the ultimate tensile strength in a three-point bending analysis, indicating increased bone strength

♂ • however, no changes are seen in trabecular or cortical bone mass and density, in osteoblast, osteocyte, or osteoclast number or surface