Phenotypes Associated with This Genotype

Genotype
MGI:3588584

• Allelic Composition: Vdr^tm1Mbd/Vdr^tm1Mbd
• Genetic Background: involves: 129S4/SvJae

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

Alopecia in 3.5 month old Vdr^tm1Mbd/Vdr^tm1Mbd (right) mice

endocrine/exocrine glands

enlarged parathyroid gland ( J:42815 )

• more than 10-fold increase in parathyroid gland size of 70-day-old mice

growth/size/body

increased heart weight ( J:78067 )

• heart weight to body weight ratio is significantly higher than control

decreased body weight ( J:42815 )

• weigh 10% less than controls by 91 days of age; weight is normal at birth

dermal cyst ( J:42815 )

postnatal growth retardation ( J:42815 )

• from 24 days of age, fail to grow as rapidly as controls

homeostasis/metabolism

increased circulating angiotensin II level ( J:78067 )

• circulating levels of angiotensin II are higher

increased circulating parathyroid hormone level ( J:42815 , J:63291 , J:78067 )

• starting on day 21, exhibit a progressive increase in parathyroid hormone levels (J:42815)

• serum PTH concentration is increased 150-fold by 3 months of age (J:78067)

• treatment with HCa-Lac (calcium, phosphorus, lactose) diet for 5 weeks lowers PTH concentration to 7-fold higher than control (J:78067)

decreased circulating calcium level ( J:42815 , J:78067 )

• become progressively hypocalcemic after day 21, maintaining ionized calcium levels about 25% lower than controls (J:42815)

• blood ionized calcium levels are decreased by 30% (J:78067)

• treatment with HCa-Lac (calcium, phosphorus, lactose) diet for 5 weeks normalizes calcium levels (J:78067)

increased circulating angiotensinogen level ( J:78067 )

• plasma angiotensinogen II levels are increased more than 2.5 fold compared to wildtype, however, expression of angiotensinogen is the same as wildtype

• on a high salt (8%) diet, plasma angiotensinogen II levels are significantly increased over treated control

• plasma angiotensinogen II levels are increased following 24 hour dehydration, however, levels for treated control exhibit a comparatively higher increase

increased circulating renin level ( J:78067 )

• renin is increased in the afferent glomerular arterioles as determined by immunoreactivity

increased urine potassium level ( J:78067 )

• mice excrete 19% more potassium in urine, however, blood potassium concentration is normal

increased urine sodium level ( J:78067 )

• mice excrete 37% more sodium in urine, however, blood sodium concentration is normal

increased renin activity ( J:78067 )

• circulating levels of angiotensin II are higher but liver levels of the angiotensinogen precursor are normal suggesting increased renin activity

skeleton

short femur ( J:42815 )

• femurs are about 15% shorter

abnormal tibia morphology ( J:42815 )

• decreased cortical width along the diaphysis and expansion and flaring of the growth plate at 35 days of age

short tibia ( J:42815 )

• tibias are about 15% shorter

increased width of hypertrophic chondrocyte zone ( J:42815 )

• 15% increase in the number of hypertrophic chondrocytes per column in the tibia and vertebra of 15 day old mice and increased hypertrophic chondrocyte zone in 35 day old growth plate

disorganized long bone epiphyseal plate ( J:42815 )

• 35 day old growth plate is disorganized with an increase in vascularity and matrix

abnormal bone mineralization ( J:42815 )

• decreased bone mineralization in 35 day old mice but not 15 day old mice

rickets ( J:42815 )

limbs/digits/tail

short femur ( J:42815 )

• femurs are about 15% shorter

abnormal tibia morphology ( J:42815 )

• decreased cortical width along the diaphysis and expansion and flaring of the growth plate at 35 days of age

short tibia ( J:42815 )

• tibias are about 15% shorter

behavior/neurological

increased fluid intake ( J:78067 )

• mice drink approximately twice as much water as controls, however, glucose and insulin levels are normal

cardiovascular system

increased heart weight ( J:78067 )

• heart weight to body weight ratio is significantly higher than control

hypertension ( J:78067 )

• mice are hypertensive with high systolic and the diastolic blood pressures caused in part by high circulating levels of renin and angiotensin II

increased systemic arterial diastolic blood pressure ( J:78067 )

• diastolic blood pressure is significantly higher (>20 mmHg) than those of wild-type littermates

increased systemic arterial systolic blood pressure ( J:78067 )

• systolic blood pressure is significantly higher (>20 mmHg) than those of wild-type littermates

renal/urinary system

increased urine potassium level ( J:78067 )

• mice excrete 19% more potassium in urine, however, blood potassium concentration is normal

increased urine sodium level ( J:78067 )

• mice excrete 37% more sodium in urine, however, blood sodium concentration is normal

polyuria ( J:78067 )

integument

dermal cyst ( J:42815 )

alopecia ( J:42815 )

• at 4 weeks of age, begin to develop perioral and periorbital alopecia

• hair loss progresses to the entire body over the next 3 months, with more rapid progression in females than males

dilated hair follicle ( J:42815 )

• dilation of the hair follicles

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
rickets		DOID:10609		J:42815