Phenotypes associated with this allele

• Allele Symbol: Cyp27b1^tm1Star
• Allele Name: targeted mutation 1, Rene St-Arnaud
• Allele ID: MGI:2182334
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cyp27b1^tm1Star/Cyp27b1^tm1Star	involves: 129S1/Sv * 129X1/SvJ	MGI:3045592
hm2	Cyp27b1^tm1Star/Cyp27b1^tm1Star	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3045622

Genotype
MGI:3045592

hm1

• Allelic Composition: Cyp27b1^tm1Star/Cyp27b1^tm1Star
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

endocrine/exocrine glands

enlarged parathyroid gland ( J:71928 )

• homozygotes display enlarged parathyroid glands (8 weeks), and secondary hyperparathyroidism

growth/size/body

decreased body size ( J:71928 )

• homozygotes display a decrease in femur length at 8 weeks

postnatal growth retardation ( J:71928 )

• homozygotes are viable and phenotypically normal at birth but fail to thrive

slow postnatal weight gain ( J:71928 )

• homozygotes display a decrease in weight gain from 3-8 weeks of age

homeostasis/metabolism

abnormal blood homeostasis ( J:71928 )

• at 3 weeks, homozygotes show lack of detectable 1,25(OH)2D3 levels

• at 8 weeks, homozygotes display elevated levels of 25(OH)D3 and very low circulating levels of 24,25(OH)2D3

increased circulating parathyroid hormone level ( J:71928 )

• homozygotes display increased PTH blood levels as early as weaning

decreased circulating calcium level ( J:71928 , J:78635 )

• at 3 weeks of age, homozygotes display hypocalcemia (J:71928)

• supplementation with 1,25(OH)2D3 normalizes the plasma Ca2+ concentration (J:78635)

• the expression of renal Ca2+ transport proteins is significantly down-regulated in agreement with a diminished Ca2+ reabsorption capacity (J:78635)

• high dietary Ca2+ intake restores the expression of renal Ca2+ transport proteins independent of 1,25(OH)2D3 and normalizes serum Ca2+ concentration (J:78635)

decreased circulating phosphate level ( J:71928 )

• young homozygotes exhibit marked hypophosphatemia which tends towards normal levels at later stages

increased circulating alkaline phosphatase level ( J:71928 )

• homozygotes display elevated serum alkaline phosphatase

skeleton

disorganized long bone epiphyseal plate ( J:71928 )

• homozygotes have expanded growth plates with disorganized cartilage layers

increased long bone epiphyseal plate size ( J:71928 )

• homozygotes have expanded growth plates with disorganized cartilage layers

abnormal long bone metaphysis morphology ( J:71928 )

• contact radiography of femurs revealed rachitic metaphyseal alterations

decreased bone mineral density of femur ( J:71928 )

• contact radiography of femurs revealed diffuse osteopenia (hypomineralization)

abnormal bone mineralization ( J:90983 , J:90984 )

• high dietary Ca2+ intake does not completely correct bone growth but cures the rickets and osteomalacia and corrects the biomechanical properties of bone tissue (J:90983)

• chronic treatment with 1,25(OH)2D3 is more effective than the high-calcium rescue diet and corrects all aspects of the mutant phenotype (J:90984)

decreased bone mineralization ( J:71928 )

• homozygotes display osteoid (unmineralized matrix) accumulation in trabecular bone due to impaired mineralization

• homozygotes display bone anomalies including rickets and osteomalacia

osteomalacia ( J:71928 )

rickets ( J:71928 )

integument

integument phenotype ( J:71928 , J:71937 )

N • consistent with symptoms of pseudovitamin D deficiency rickets, homozygotes display no alopecia (J:71928)

N • homozygotes do not exhibit alopecia (J:71937)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
rickets		DOID:10609		J:71928 , J:71937 , J:78635 , J:90983 , J:90984

Genotype
MGI:3045622

hm2

• Allelic Composition: Cyp27b1^tm1Star/Cyp27b1^tm1Star
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

growth/size/body

decreased body size ( J:89330 )

• on a 1.3% calcium diet, differences in body size are observed only after 6 weeks

postnatal growth retardation ( J:89330 )

• a 2.4% calcium rescue diet prevents any decline in growth rate

homeostasis/metabolism

impaired skin barrier function ( J:89330 )

• homozygotes display normal basal transepidermal water loss rates

• following tape stripping, homozygotes show a significant delay in the recovery of barrier function

• this delay is associated with reduced lamellar body secretion and abnormal restoration of the epidermal calcium gradient following barrier disruption

• high dietary Ca2+ intake or exogenous application of 1,25(OH)2D fail to normalize these findings

integument

abnormal keratinocyte differentiation ( J:89330 )

• homozygotes show a reduction in the expression of involucrin, filaggrin and loricrin, and a decrease in the number of keratohyalin granules (both the F- and L-type) in the upper layers of the epidermis

impaired skin barrier function ( J:89330 )

• homozygotes display normal basal transepidermal water loss rates

• following tape stripping, homozygotes show a significant delay in the recovery of barrier function

• this delay is associated with reduced lamellar body secretion and abnormal restoration of the epidermal calcium gradient following barrier disruption

• high dietary Ca2+ intake or exogenous application of 1,25(OH)2D fail to normalize these findings

cellular

abnormal keratinocyte differentiation ( J:89330 )

• homozygotes show a reduction in the expression of involucrin, filaggrin and loricrin, and a decrease in the number of keratohyalin granules (both the F- and L-type) in the upper layers of the epidermis