Biomedical subjects

R J Iorio

Publications and source records attributed to R J Iorio.

11 recordsLinked to original sources

PubMed1992

Craniometric measurements of craniofacial malformations in the X-linked hypophosphatemic (Hyp) mouse on two different genetic backgrounds: C57BL/6J and B6C3H.

This study reports data on craniometric measurements in the X-linked hypophosphatemic (Hyp) mouse on two different genetic backgrounds: C57BL/6J and B6C3H. Heads of normal females "+/+," normal males "+/Y," heterozygous mutant females "Hyp/+," and hemizygous mutant males "Hyp/Y" for each genetic background were examined. Data were collected via skull measurements. On a C57BL/6J background, the neurocranium of mutants "Hyp/+" and "Hyp/Y" was shorter and slightly higher than in normal counterparts. On a B6C3H background, mutant mice "Hyp/+" and "Hyp/Y" were shorter in neurocranial length than in normal counterparts. Viscerocranial height was larger in "Hyp/Y" than in normal counterparts. No differences in neurocranial and mandibular height were found. Mutant mice on a C57BL/6J background were compared to mutant mice on a B6C3H background. No differences in neurocranial length were found. Cranial length was shorter in "Hyp/Y" on C57BL/6J than in "Hyp/+" on B6C3H. Facial length parameters were shorter in "Hyp/Y" on C57BL/6J than in "Hyp/Y" and "Hyp/+" mutant mice on B6C3H. Mandibular length was shorter in "Hyp/Y" on C57BL/6J than in "Hyp/+" on C57BL/6J and both mutant mice ("Hyp/Y" and "Hyp/+") on a B6C3H background. The results of this study indicate that craniofacial growth is less affected in mutant mice on a B6C3H genetic background than in mutant mice on a C57BL/6J genetic background.

Animals↗

PubMed1987

Mineral uptake by the femora of older female X-linked hypophosphatemic (HYP) mice but not older male HYP mice.

X-linked hypophosphatemic (Hyp) mice are a model of human sex-linked vitamin D-resistant rickets. Young adult Hyp mice are characterized by osteomalacia and decreased bone mineral content. However, older heterozygous Hyp female mice increase in bone mineral content with age so that by one year of age the bone mass/mm femoral length equals or exceeds normal females. To test for the occurrence of this mineral accretion in Hyp male mice and in homozygous Hyp female mice, femora from all 3 Hyp genotypes as well as normal male and female mice were analyzed at various ages from one to 52 weeks of age. Compared to normal mice, all three Hyp genotypes were depressed in bone ash, femoral length, and ash/length ratio at 13 weeks of age. After that age the femora of both heterozygous and homozygous Hyp females showed a slow mineral accretion and, by 52 weeks of age, a normal ash/length ratio. However, the femora of Hyp males, as well as those of normal males, failed to increase in bone mineral content or ash/length ratio after 13 weeks of age. The differences between male and female Hyp mice could not be explained by differences in the plasma levels of calcium, phosphate, or alkaline phosphatase. Increased bone mineral content in older Hyp mice was seen in both heterozygous and homozygous females but not in hemizygous males. Thus, the basis for this increase is not incomplete dominance of the Hyp gene in females nor the Lyon hypothesis. The accretion of mineral in older female Hyp mice despite lifelong reduced plasma phosphate levels suggests that there are factors other than phosphate that also regulate mineral accretion in this bone disease.

Aging↗

PubMed1984

A role for the intestine in the bone disease of juvenile X-linked hypophosphatemic mice: malabsorption of calcium and reduced skeletal mineralization.

Low duodenal vitamin D-dependent calcium-binding protein has been reported in juvenile Hyp mice. Levels of this protein improved in adult Hyp mice. This led to the search for possible abnormal intestinal calcium absorption in juvenile Hyp mice and for evidence that calcium malabsorption, if present, would exacerbate the bone disease. A balance study was performed in 10 sets of normal and Hyp male mice at 5 and 12 weeks of age. Twelve-week-old Hyp mice had balances (24-h intake minus excretion) of Ca, P, Mg, Na, and K that were not significantly different from those of 12-week-old normal mice. However, 5-week-old Hyp mice had a significantly lower balance of Ca with higher fecal Ca and lower urinary Ca. No balance was also lower due to higher fecal Na. The balances of P, Mg, and K were not significantly affected in young Hyp mice. Growth and mineralization of the femur were compared in normal and heterozygous female Hyp mice from 3.5-46 weeks of age. The femora of Hyp mice gained ash weight at a rate comparable to that for normal mice, except for a lag between 3.5 and 7 weeks. There was life-long hypophosphatemia and elevated plasma alkaline phosphatase. It was concluded that the period of low levels of duodenal vitamin D-dependent calcium-binding protein was associated with low intestinal absorption and low skeletal mineralization. This dysfunction of the intestine in juvenile, rapidly growing Hyp mice may exacerbate the bone disease.

Alkaline Phosphatase↗

PubMed1982

Deficient nasal bone growth in the X-linked hypophosphataemic (HYP) mouse and its implication in craniofacial growth.

Mice bearing the mutant Hyp gene are characterized by craniofacial abnormalities secondary to their metabolic bone disease. X-ray cephalograms were taken of 40 normal and 29 Hyp mice at 1, 2, 3 and 4 weeks of age in one group and at weeks 6, 9 and 12 in a second. Hyp mice exhibited shorter skulls, shorter mandibles antero-posteriorly and a compressed upper face height. Both the fronto-nasal and the premaxillo-maxillary sutures in the Hyp mice were deformed and failed to close by 12 weeks of age. The deficient linear growth of the nasal bone was the most important measured variable contributing to the overall difference in the skull morphology between Hyp and normal mice. Thus this animal model is promising for elucidating the regulatory mechanisms affecting craniofacial growth.

Animals↗

PubMed1981

Craniosynostosis in vitamin D-resistant rickets. A mouse model.

Craniosynostosis and associated craniofacial deformities, such as frontal bossing, often occur as symptoms of vitamin D-resistant rickets in children. Similar skull deformities develop in mice with X-linked dominant hypophosphatemia, the most common form of vitamin D-resistant rickets. These mice have a short, wide, high neurocranium, which suggested an inhibition of coronal suture growth. To study this question, we compared histologically the postnatal development of the coronal sutures in normal and hypophosphatemic mice between 1 and 13 weeks of age. Premature fusion of the coronal suture occurred in hypophosphatemic mice by 4 weeks of age. The proportion of the suture obliterated by bone varied among individual animals, but craniosynostosis was present in all animals studied at 4 weeks and older. Fusion of the coronal suture did not occur through 13 weeks of age in any of the normal mice studied. The x-linked hypophosphatemic mouse is an animal model that can be used to study the role of vitamin D-resistant rickets in the development of craniosynostosis, to relate craniosynostosis to the development of associated skull deformities, and to test new treatment procedures.

Animals↗

PubMed1980

Craniometric measurements of craniofacial malformations in mice with X-linked, dominant hypophosphatemia (vitamin D-resistant rickets).

Skulls of hemizygous male and heterozygous female C57CL/6J mice affected with X-linked, dominant hypophosphatemia ("Hyp" mutant; C57BL/6J-Hyp)--vitamin D-resistant rickets (VDRR)--were compared grossly and by craniometry with skulls of normal C57BL/6J mice to describe the malformation that accompanies this condition. In mutant males a slight retardation in mandibular growth is observed. The neurocranium of mutants is shorter, more domed, and exhibits frontal and occipital bossing. Retardation in growth of the viscerocranium occurs. A characteristic protrusion of the frontopremaxillary suture is present at the junction of the neural and facial skulls. No differences in width are demonstrable. The malformation in mutant females is similar to that found in males but is less pronounced. The craniofacial malformations in humans with VDRR are generally similar to those described in the C57BL/6J-Hyp mouse.

Animals↗

PubMed1979