Mouse Genome Informatics
tg
    Tg(APOE-FGF23*R176Q)#Ack/0
involves: C57BL/6J * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
growth/size

craniofacial

endocrine/exocrine glands
• parathyroids become progressively enlarged over time
• secondary hyperparathyroidism

hematopoietic system

homeostasis/metabolism
• serum calcium levels are slightly diminished
• urinary calcium excretion is decreased, indicating increased renal tubular calcium reabsorption in response to circulating parathyroid hormone (PTH)
• decrease in renal tubular reabsorption of phosphate
• low serum levels of 1,25-dihydroxyvitamin D3
• urinary calcium excretion is decreased, indicating increased renal tubular calcium reabsorption in response to circulating parathyroid hormone (PTH)
• increase in serum alkaline phosphatase activity

immune system

limbs/digits/tail

renal/urinary system
• urinary calcium excretion is decreased, indicating increased renal tubular calcium reabsorption in response to circulating parathyroid hormone (PTH)
• decrease in renal tubular reabsorption of phosphate
• urinary calcium excretion is decreased, indicating increased renal tubular calcium reabsorption in response to circulating parathyroid hormone (PTH)

skeleton
• mutants exhibit mineralizing enthesopathy of the Achilles insertion (abnormal bony projections at the attachment of the tendon) as indicated by an expansion of type II collagen expressing mineralizing fibrochondrocytes in the Achilles insertion into the posterior and medial processes of the calcaneus at 12 weeks of age
• expanded calcification of the entheses during the period of long bone growth
• mutants exhibit a round back
• trabecular volume is increased, however mineralized trabeculae are much less numerous than in wild-type mice
• expansion of fibrochondrocytes (type II collagen expressing, showing alkaline phosphatase activity, and proteoglycan-secreting fibrochondrocytes) at the Achilles and plantar facial insertions
• mutants exhibit mineralizing enthesopathy of plantar facial insertion (abnormal bony projections at the attachment of the ligament) as indicated by an expansion of type II collagen expressing fibrochondrocytes at the plantar fascia ligament attachment
• growth plates are wider, more disorganized and less well mineralized, consistent with advanced rickets
• mutants exhibit significant unmineralized osteoid bone
• tibias of 1-2 month old mutants show wider, unmineralized growth plate and epiphyseal region of femurs show reduced mineralization
• osteomalacic changes are seen in trabecular and cortical bone due to increased amounts of unmineralized osteoid
• growth plates are wider, more disorganized and less well mineralized, consistent with advanced rickets
• low osteoclast number and the persistence of aggrecan expression and chondrocytes in the bone trabeculae indicating diminished bone resorption

muscle
• mutants exhibit mineralizing enthesopathy of the Achilles insertion (abnormal bony projections at the attachment of the tendon) as indicated by an expansion of type II collagen expressing mineralizing fibrochondrocytes in the Achilles insertion into the posterior and medial processes of the calcaneus at 12 weeks of age
• expanded calcification of the entheses during the period of long bone growth

Mouse Models of Human Disease
OMIM IDRef(s)
Hypophosphatemic Rickets, Autosomal Dominant; ADHR 193100 J:93981
Hypophosphatemic Rickets, Autosomal Recessive, 2; ARHR2 613312 J:192371
Hypophosphatemic Rickets, X-Linked Dominant; XLHR 307800 J:93981