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Deletion of the MBII-85 snoRNA Gene Cluster in Mice Results in Postnatal Growth Retardation
Open accessAbstract
Prader-Willi syndrome (PWS [MIM 176270]) is a neurogenetic disorder characterized by decreased fetal activity, muscular hypotonia, failure to thrive, short stature, obesity, mental retardation, and hypogonadotropic hypogonadism. It is caused by the loss of function of one or more imprinted, paternally expressed genes on the proximal long arm of chromosome 15. Several potential PWS mouse models involving the orthologous region on chromosome 7C exist. Based on the analysis of deletions in the mouse and gene expression in PWS patients with chromosomal translocations, a critical region (PWScr) for neonatal lethality, failure to thrive, and growth retardation was narrowed to the locus containing a cluster of neuronally expressed MBII-85 small nucleolar RNA (snoRNA) genes. Here, we report the deletion of PWScr. Mice carrying the maternally inherited allele (PWScr(m-/p+)) are indistinguishable from wild-type littermates. All those with the paternally inherited allele (PWScr(m+/p-)) consistently display postnatal growth retardation, with about 15% postnatal lethality in C57BL/6, but not FVB/N crosses. This is the first example in a multicellular organism of genetic deletion of a C/D box snoRNA gene resulting in a pronounced phenotype.
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Cites
Genome Organization, Function, and Imprinting in Prader-Willi and Angelman Syndromes
Nicholls, R. D., & Knepper, J. L. (2001) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.2.1.153 · Cited by 625
Whittington, J. E., Holland, A. J., Webb, T., Butler, J., Clarke, D., & Boer, H. (2001) · Journal of Medical Genetics · doi:10.1136/jmg.38.11.792 · Cited by 451
Cited by
Long Noncoding RNAs with snoRNA Ends
Yin, Q.-F., Yang, L., Zhang, Y., Xiang, J.-F., Wu, Y.-W., Carmichael, G. G., & Chen, L.-L. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.07.033 · Cited by 444
The comorbidity of autism with the genomic disorders of chromosome 15q11.2-q13
Hogart, A., Wu, D., LaSalle, J. M., & Schanen, N. C. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.08.011 · Cited by 351
Functional diversity of small nucleolar RNAs
Bratkovič, T., Božič, J., & Rogelj, B. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkz1140 · Cited by 272
Schaller, F., Watrin, F., Sturny, R., Massacrier, A., Szepetowski, P., & Muscatelli, F. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq424 · Cited by 234
A Prader–Willi locus lncRNA cloud modulates diurnal genes and energy expenditure
Powell, W. T., Coulson, R. L., Crary, F. K., Wong, S. S., Ach, R. A., Tsang, P., Alice Yamada, N., Yasui, D. H., & LaSalle, J. M. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt281 · Cited by 173
Metadata
- Authors
- Skryabin, B. V., Gubar, L. V., Seeger, B., Pfeiffer, J., Handel, S., Robeck, T., Karpova, E., Rozhdestvensky, T. S., & Brosius, J.
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2007-12-28
- Volume
- 3
- Issue
- 12
- Pages
- e235
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- OpenAlex
- W1967481218
- Cited by
- 177
- References
- 2
- FWCI
- 5.86
- Type
- journal article
- Language
- en
- Open access
- gold
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- Skryabin, B. V., Gubar, L. V., Seeger, B., Pfeiffer, J., Handel, S., Robeck, T., Karpova, E., Rozhdestvensky, T. S., & Brosius, J. (2007). Deletion of the MBII-85 snoRNA Gene Cluster in Mice Results in Postnatal Growth Retardation. PLoS Genetics. https://doi.org/10.1371/journal.pgen.0030235
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