Hostname: page-component-848d4c4894-sjtt6 Total loading time: 0 Render date: 2024-07-01T13:20:15.821Z Has data issue: false hasContentIssue false
  • English
  • Français

Parental origin of mutant allele does not explain absence of gene dose in X-linked Hyp mice

Published online by Cambridge University Press:  14 April 2009

Z. Q. Qiu ,
H. S. Tenenhouse  and
C. R. Scriver
Z. Q. Qiu
Affiliation:
MRC Genetics Group, Departments of Biology and Pediatrics, McGill University, Montreal, Quebec, Canada
H. S. Tenenhouse
Affiliation:
MRC Genetics Group, Departments of Biology and Pediatrics, McGill University, Montreal, Quebec, Canada
C. R. Scriver*
Affiliation:
MRC Genetics Group, Departments of Biology and Pediatrics, McGill University, Montreal, Quebec, Canada
*
* Harriet S. Tenenhouse, MRC Genetics Group, Montreal Children's Hospital, 2300 Tupper Street, Montreal, Quebec H3H 1P3, Canada.

Summary

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The expectation for a gene dose effect in an X-linked phenotype is that the corresponding metrical trait in heterozygous females will lie between values for affected hemizygous males and unaffected males and females. We made sequential measurements (at 30, 60, 90, 120 and 150 days) of serum phosphate concentration and tail length in mice with X-linked hypophosphatemia (genotypes: Hyp/Y, Hyp/+ and Hyp/Hyp) and in their normal litter-mates (genotypes: +/Y, +/+). We also measured renal mitochondrial 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase) activity in 5 to 7-month-old mice fed control and low phosphate diets and representing all five genotypes. The animals were obtained by controlled breeding under uniform environmental conditions. The mutant animals all had uniformly and significantly lower serum phosphate levels, shorter tail length and higher 24-hydroxylase activity relative to unaffected litter-mates. There was no evidence of a gene dose effect because values were not significantly different among the three mutant genotypes. We also studied the influence of gamete of origin on serum phosphate, tail length and renal mitochondrial 24-hydroxylase activity in the Hyp/+ offspring of affected males (Hyp/Y) or affected females (Hyp/+ or Hyp/Hyp). We found no effect on the distribution of trait values. We conclude that parental origin of mutant allele does not explain the absence of a gene dose effect in Hyp mice.

Type
Research Article
Information
Genetics Research , Volume 62 , Issue 1 , August 1993 , pp. 39 - 43
Copyright
Copyright © Cambridge University Press 1993

References

Arnaud, C., Glorieux, F. & Scriver, C. R. (1971). Serum parathyroid hormone in X-linked hypophosphatemia. Science 173, 845–847.CrossRefGoogle ScholarPubMed
Broadhead, D. M., Kirk, J. M., Burt, A. J., Gupta, V., Ellis, P. M. & Besley, G. T. N. (1986). Full expression of Hunter's disease in a female with an X-chromosome deletion leading to non-random inactivation. Clinical Genetics 30, 392–398.Google Scholar
Coleclough, C., Perry, R. P., Karjalainen, K. & Weigert, M. (1981). Aberrant rearrangements contribute significantly to the allelic exclusion of immunoglobulin gene expression. Nature 290, 372–378.CrossRefGoogle Scholar
Cowgill, L. D., Goldfarb, S., Lau, K., Slatopolsky, E. & Agus, Z. S. (1979). Evidence for an intrinsic renal tubular defect in mice with genetic hypophosphatemic rickets. Journal of Clinical Investigations 63, 1203–1210.CrossRefGoogle ScholarPubMed
Econs, M. J., Barker, D. F., Speer, M. C., Pericak-Vance, M. A., Fain, P. R. & Drezner, M. K. (1992). Multilocus mapping of the X-linked hypophosphatemic rickets gene. Journal of Clinical Endocrinology and Metabolism 75, 201–206.Google ScholarPubMed
Eicher, E. M., Southard, J. L., Scriver, C. R. & Glorieux, F. H. (1976). Hypophosphatemia: Mouse model for human familial hypophosphatemic (vitamin D-resistant) rickets. Proceedings of the National Academy of Sciences 73,4667–4671.CrossRefGoogle ScholarPubMed
Herskowitz, I. (1987). Functional inactivation of genes by dominant negative mutations. Nature 329, 219–222.Google Scholar
Jones, G., Vriezen, D., Lohnes, D., Palda, V. & Edwards, N. S. (1987). Side chain hydroxylation of vitamin D3 and its physiological implications. Steroids 49, 29–53.CrossRefGoogle ScholarPubMed
Kay, G., Thakker, R. V. & Rastan, S. (1991). Determination of a molecular map position for Hyp using a new interspecific backcross produced by in vitro fertilization. Genomics 11, 651–657.Google Scholar
Lyon, M. F. (1988). X-chromosome inactivation and the location and expression of X-linked genes. American Journal of Human Genetics 42, 8–16.Google ScholarPubMed
Meyer, R. A. Jr, Meyer, M. H. & Gray, R. W., (1989 a). Parabiosis suggests a humoral factor is involved in Xlinked hypophosphatemia in mice. Journal of Bone and Mineral Research 4, 493–500.CrossRefGoogle ScholarPubMed
Meyer, R. A. Jr, Tenenhouse, H. S., Meyer, M. H. & Klugerman, A. H., (1989 b). The renal phosphate transport defect in normal mice parabiosed to X-linked hypo phosphatemic mice persists after para thy roidectomy. Journal of Bone and Mineral Research 4, 523–532.Google Scholar
Nesbitt, T., Coffman, T. M., Griffiths, R. & Drezner, M. K. (1992). Cross-transplantation of kidneys in normal and Hyp mice: Evidence that the Hyp phenotype is unrelated to an intrinsic renal defect. Journal of Clinical Investigation 89, 1453–1459.CrossRefGoogle Scholar
Qiu, Z. Q., Kalavritinos, G., Tenenhouse, H. S. & Scriver, C. R. (1992). Gamete-of-origin dependent effects do not explain unusual gene dosage in Hyp mice with X-linked hypophosphatemia (XLH). American Journal of Human Genetics 51, A174 (Abstract).Google Scholar
Rasmussen, H. & Tenenhouse, H. S. (1989). Hypophosphatemias. In The Metabolic Basis of Inherited Disease (ed. R.Scriver, C., Beaudet, A. L., Sly, W. S. and Valle, D.), pp. 2581–2601. New York: McGraw Hill Book Co.Google Scholar
Reid, I. R., Murphy, W. A., Hardy, D. C., Teitelbaum, S. L., Bergfeld, M. A. & Whyte, M. P. (1991). X-linked hypophosphatemia: skeletal mass in adults assessed by histomorphometry, computed tomography, and absorptiometry. American Journal of Medicine 90, 63–69.CrossRefGoogle ScholarPubMed
Sapienza, C., Peterson, A. C., Rossant, J. & Balling, J. (1987). Degree of methylation of transgenes is dependent on game of origin. Nature 328, 251–254.CrossRefGoogle Scholar
Scriver, C. R., Tenenhouse, H. S. & Glorieux, F. H. (1991). Commentary. X-linked hypophosphatemia: An appreciation of a classic paper and a survey of progress since 1958. Medicine 70, 218–228.Google Scholar
Scriver, C. R. & Tenenhouse, H. S. (1990). Conserved loci on the X chromosome confer phosphate homeostasis in mice and humans. Genetical Research 56, 141–152.CrossRefGoogle ScholarPubMed
Shields, E. D., Scriver, C. R., Reade, T. et al. (1990). Xlinked hypophosphatemia: The mutant gene is expressed in teeth as well as in kidney. American Journal of Human Genetics 46, 434–442.Google ScholarPubMed
Tenenhouse, H. S. & Jones, G. (1987). Effect of the X-linked Hyp mutation and vitamin D status on induction of renal 25-hydroxyvitamin D3-24-hydroxylase. Endocrinology 120, 609–616.CrossRefGoogle ScholarPubMed
Tenenhouse, H. S. & Jones, G. (1990). Abnormal regulation of renal vitamin D catabolism by dietary phosphate in murine X-linked hypophosphatemic rickets. Journal of Clinical Investigation 85, 1450–1455.CrossRefGoogle ScholarPubMed
Tenenhouse, H. S. & Scriver, C. R. (1978). The defect in transcellular transport of phosphate in the nephron is located in brush-border membranes in X-linked hypophosphatemia (Hyp mouse model). Canadian Journal of Biochemistry 56, 640–646.CrossRefGoogle ScholarPubMed
Tenenhouse, H. S. & Scriver, C. R. (1992). X-linked hypophosphatemia. A phenotype in search of a cause. International Journal of Biochemistry 1A, 685–691.CrossRefGoogle Scholar
Tenenhouse, H. S., Yip, A. & Jones, G. (1988). Increased renal catabolism of 1,25-dihydroxyvitamin D3 in murine X-linked hypophosphatemic rickets. Journal of Clinical Investigation 81, 461–465.Google Scholar
Thakker, R. V., Davies, K. E., Read, A. P. et al. (1990). Linkage analysis of two cloned DNA sequences, DXS197 and DXS207, in hypophosphatemic rickets families. Genomics 8, 189–193.Google Scholar
Winters, R. W., Graham, J. B., Williams, T. F., McFalls, V. W. & Burnett, C. H. (1958). A genetic study of familial hypophosphatemia and vitamin D-resistant rickets with a review of the literature. Medicine 37, 97–142.Google Scholar