MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gwynn, B.
Right arrow Articles by Birkenmeier, E. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gwynn, B.
Right arrow Articles by Birkenmeier, E. H.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 1998, p. 6474-6481, Vol. 18, No. 11
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Intracisternal A-Particle Element Transposition into the Murine beta -Glucuronidase Gene Correlates with Loss of Enzyme Activity: a New Model for beta -Glucuronidase Deficiency in the C3H Mousedagger

Babette Gwynn,1,* Kira Lueders,2 Mark S. Sands,3 and Edward H. Birkenmeier1

The Jackson Laboratory, Bar Harbor, Maine 046091; Laboratory of Biochemistry, National Cancer Institute, Bethesda, Maryland 20892-42552; and Washington University School of Medicine, St. Louis, Missouri 631103

Received 5 January 1998/Returned for modification 28 April 1998/Accepted 12 August 1998

The severity of human mucopolysaccharidosis type VII (MPS VII), or Sly syndrome, depends on the relative activity of the enzyme beta -glucuronidase. Loss of beta -glucuronidase activity can cause hydrops fetalis, with in utero or postnatal death of the patient. In this report, we show that beta -glucuronidase activity is not detectable by a standard fluorometric assay in C3H/HeOuJ (C3H) mice homozygous for a new mutation, gusmps2J. These gusmps2J/gusmps2J mice are born and survive much longer than the previously characterized beta -glucuronidase-null B6.C-H-2bm1/ByBir-gusmps (gusmps/gusmps) mice. Northern blot analysis of liver from gusmps2J/gusmps2J mice demonstrates a 750-bp reduction in size of beta -glucuronidase mRNA. A 5.4-kb insertion in the Gus-sh nucleotide sequence from these mice was localized by Southern blot analysis to intron 8. The ends of the inserted sequences were cloned by inverse PCR and revealed an intracisternal A-particle (IAP) element inserted near the 3' end of the intron. The sequence of the long terminal repeat (LTR) regions of the IAP most closely matches that of a composite LTR found in transposed IAPs previously identified in the C3H strain. The inserted IAP may contribute to diminished beta -glucuronidase activity either by interfering with transcription or by destabilizing the message. The resulting phenotype is much less severe than that previously described in the gusmps/gusmps mouse and provides an opportunity to study MPS VII on a genetic background that clearly modulates disease severity.

* Corresponding author. Mailing address: The Jackson Laboratory, 600 Main St., Bar Harbor, ME 04609. Phone: (207) 288-6392. Fax: (207) 288-6073. E-mail: bfg{at}aretha.jax.org.

dagger This paper is dedicated to the memory of Edward Birkenmeier, a fine scientist and good friend, for whom every mutant mouse was an opportunity and every aspect of biology a joy.

Molecular and Cellular Biology, November 1998, p. 6474-6481, Vol. 18, No. 11
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 1998 by the American Society for Microbiology. All rights reserved.