Mouse Genome Informatics
hm
    Vdrtm1Ska/Vdrtm1Ska
involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• most mice died within 15 weeks of birth (J:42054)
• die at 6 - 7 weeks of age when fed a 0.02% calcium diet (J:69822)

craniofacial

growth/size/body
• weigh about 50% of wild-type at 6 weeks of age (J:42054)
• mice weigh about 30% less than controls around 86 days of age (J:72578)
• beginning after weaning (J:42054)

skeleton
• appearance is similar to that of advanced rickets with widening of the epiphysis, thinning of the cortex, and fraying, cupping, and widening of the metaphysis
• appearance is similar to that of advanced rickets with widening of the epiphysis, thinning of the cortex, and fraying, cupping, and widening of the metaphysis
• widened in the tibia and fibula at 13 weeks of age
• layers of cartilage are wider with inadequate mineralization
• fraying, cupping, and widening of the metaphysis are seen in the tibia and fibula at 13 weeks of age
• about a 40% reduction is detected at 7 weeks of age, but bone density is similar to wild-type prior to weaning (J:42054)
• mean femoral calcium levels are reduced by about 30% (J:72578)
• thinning in the tibia and fibula at 13 weeks of age
• bone surfaces in cancellous bone are surrounded by numerous osteoblastic cells
• osteoclast numbers are similar to wild-type
• in bone adjacent to the growth plates the extent and width of osteoid seems is increased and bone surfaces are surrounded by numerous osteoblastic cells
• impaired bone formation after weaning
• low bone calcium when fed a normal diet
• bone calcium levels are similar to wild-type when mice are fed a high-lactose and are partially restored in mice on a high-fat diet
• is observed in these mice when fed a normal chow diet (J:72578)
• develop after 3 weeks of age (J:110729)

reproductive system
• only primary and secondary follicles are seen at 7 weeks of age (J:42054)
• at 7 weeks of age the uterus appears immature and hypoplastic; however uterine development is normal until 4 - 5 weeks of age (J:42054)
• treatment with estrogen increases uterine size (J:42054)
• sperm counts were approximately half of those of wild-type and heterozygous mice at 10 weeks of age (J:83237)
• normal sperm counts in mice supplemented with estradiol (J:83237)
• dilation of tubules at 10 weeks of age with further dilation and atrophy at 15 weeks of age (J:83237)
• seminiferous tubules of mice supplemented with estradiol are histologically indistinct from wild-type (J:83237)
• testicular weight was increased at 10 weeks of age relative to wild-type, however it was normal at 15 weeks of age (J:83237)
• females did not show labial swelling or reddening of vaginal membranes (J:83237)
(J:42054)
• when maintained on a nonpurified diet from weaning only 14% are fertile (J:69822)
• however, when fed a 10% lactose diet or on a high calcium diet all mice are fertile and litter size is similar to wild-type (J:69822)
• fertility is reduced when mice are on a 0.47% calcium diet (J:69822)
(J:42054)
• when maintained on a nonpurified diet from weaning only 14% are fertile (J:69822)
• however, when fed a 10% lactose diet or on a high calcium diet all mice are fertile (J:69822)
• fertility is reduced when mice are on a 0.47% calcium diet (J:69822)
• increased motility observed after supplementatiom with estradiol and, to a lesser extent, calcium (J:83237)

homeostasis/metabolism
• high serum osteocalcin levels when fed a normal diet
• normal levels at 3 weeks of age
• levels were twice those of wild-type between 8 and 12 weeks of age
• normal levels at 3 weeks of age
• 5- to 10-fold increase relative to wild-type at 8 weeks of age through 12 weeks of age
• develops by 4 weeks of age (1 week after weaning) (J:42054)
• when fed a nonpurified, 0.47% calcium, or 0.02% calcium diet (J:69822)
• serum calcium levels are slightly but not significantly lower when mice are on high calcium, medium calcium, or 10% lactose diet (J:69822)
• mean serum calcium levels on a normal chow diet are 6.0 mg/dl compared to 8.6 in wild-type controls (J:72578)
• develops by 4 weeks of age
• serum activity is significantly elevated by 4 weeks of age
• serum levels of 1alpha,25-dihydroxyvitamin D3 are increased about 50 fold and serum levels of 25-dihydroxyvitamin D3 are decreased (J:71459)
• serum levels of 1alpha,25-dihydroxyvitamin D3 are increased about 10-fold and serum levels of 24,25-dihydroxyvitamin D3 are decreased to almost undetectable levels at 4 and 7 weeks of age
• however, these levels are similar to wild-type prior to weaning

immune system
• impaired chemotaxis capacity in response to casain or fnlpntl in mice on a normal diet but not in mice fed a high-lactose or high-fat diet
• anti-CD3 stimulated proliferation is impaired in splenocytes from mice fed a normal diet but not in mice fed a high-fat diet
• highly resistant to streptozotocin induced diabetes when fed a normal diet but not when fed a high-lactose or high-fat diet
• after 17 days of MC903 application to the ears

digestive/alimentary system
• in the sigmoid colon, the proliferative compartment is enlarged towards the upper part of the crypt and density of PCNA staining is increased
• in the descending colon more cells are positive for DNA oxidation and increased cell proliferation is seen
• mice have about a 3-fold lower ability to absorb calcium through the gut after being maintained on a low calcium diet

endocrine/exocrine glands
• in the sigmoid colon, the proliferative compartment is enlarged towards the upper part of the crypt and density of PCNA staining is increased
• only primary and secondary follicles are seen at 7 weeks of age (J:42054)
• dilation of tubules at 10 weeks of age with further dilation and atrophy at 15 weeks of age (J:83237)
• seminiferous tubules of mice supplemented with estradiol are histologically indistinct from wild-type (J:83237)
• testicular weight was increased at 10 weeks of age relative to wild-type, however it was normal at 15 weeks of age (J:83237)

limbs/digits/tail
• appearance is similar to that of advanced rickets with widening of the epiphysis, thinning of the cortex, and fraying, cupping, and widening of the metaphysis
• appearance is similar to that of advanced rickets with widening of the epiphysis, thinning of the cortex, and fraying, cupping, and widening of the metaphysis

hematopoietic system
• impaired chemotaxis capacity in response to casain or fnlpntl in mice on a normal diet but not in mice fed a high-lactose or high-fat diet
• anti-CD3 stimulated proliferation is impaired in splenocytes from mice fed a normal diet but not in mice fed a high-fat diet

integument
N
• topical application of MC903 does not create an atopic dermatitis-like (AD) phenotype in null mice as in Vdrtm1Pcn homozygotes (J:111828)
• after 17 days of MC903 application to the ears
• develops by 7 weeks of age (J:42054)
• mice develop a progressive form of alopecia that occurs with little skin inflammation (J:67149)
• seen in some mice by 6 weeks of age and in most by 3 months of age with near total hair loss by 8 months of age (J:110729)
• at 3 weeks, hair follicles lacking hair shafts are dilated
• decreased hair follicle proliferation
• few whiskers present at 7 weeks of age
• observed with thin hair sheaths at 3 weeks of age and contain tissue debris
• cyst size increases with age
• increase in the number of small dense granules with few or no surrounding keratin bundles and apparent absence of mature keratohyalin granules
• at 1 week of age, expression of differentiation markers in the epidermis is decreased compared to wild-type, but this difference is reduced by 3 weeks of age

cellular
• impaired chemotaxis capacity in response to casain or fnlpntl in mice on a normal diet but not in mice fed a high-lactose or high-fat diet
• anti-CD3 stimulated proliferation is impaired in splenocytes from mice fed a normal diet but not in mice fed a high-fat diet

Mouse Models of Human Disease
OMIM IDRef(s)
Osteoporosis 166710 J:83237
Vitamin D-Dependent Rickets, Type 2A; VDDR2A 277440 J:42054 , J:83237