Characterization of two transgene-induced mutations of the mouse: Sl(tg) and Del(19)TgN8052.
dc.contributor.author | Keller, Scott Alan | en_US |
dc.contributor.advisor | Meisler, Miriam | en_US |
dc.date.accessioned | 2014-02-24T16:18:25Z | |
dc.date.available | 2014-02-24T16:18:25Z | |
dc.date.issued | 1994 | en_US |
dc.identifier.other | (UMI)AAI9423226 | en_US |
dc.identifier.uri | http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:9423226 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/103970 | |
dc.description.abstract | In this dissertation I describe two lines of mice with transgene-induced mutations. The first is a mutation of steel ($Sl\sp{tg}$), a gene required for normal development of melanoblasts, primordial germ cells, and hematopoietic stem cells. The second is a deletion of chromosome 19 (Del(19)TgN8052) which includes the Pax-2 gene, a member of a developmentally important family of transcription factors. This mutation results in abnormalities of renal development. Line Tg6208 carries a transgene-induced mutation of steel. The mutation results in diluted pigmentation and reduced testes weight, similar to previously identified steel mutations. The genotypes of 60 offspring from the cross Tg6208 x C57BL/6J were determined using a restriction fragment length variation for the Pah gene. The transgene failed to recombine with Pah in all 60 offspring examined, indicating that the transgene is within 4.9 cM of Pah (p $<$ 0.05) consistent with insertion at the steel locus on chromosome 10. The transgene-induced mutation failed to complement the mutations Sl and $Sl\sp{pan}$. The mutation in line Tg8052 results in abnormal kidney development, reduced body size and kidney size, reduced viability in hemizygotes, and prenatal death in homozygotes. Abnormalities of the kidneys observed in transgenic animal of this line include reduced kidney size (4.8 $\pm$ 0.7 mg per g body weight versus 6.2 $\pm$ 0.8 mg per g for nontransgenic siblings), cystic kidneys, and renal aplasia. The fraction of transgenic mice produced by crossing Tg8052 hemizygotes to C57BL/6J is significantly less than 50%, and is reduced with increasing numbers of generations crossed to C57BL/6J. Southern blot analysis of (Tg8052 x SPRET)F$\sb1$ DNA using a probe for Pax-2 showed that Pax-2 is deleted from the transgenic chromosome. Deleted loci include Scd1 (D19Nds1), D19Mit11, D19Mit17, D19Mit24, D19Mit27, and ep. The centromere-distal breakpoint of the deletion was cloned, and a polymorphic microsatellite marker, D19Umi1, was identified in the cloned DNA. These observations suggest that abnormal kidney development results from Pax-2 haploinsufficiency. | en_US |
dc.format.extent | 106 p. | en_US |
dc.subject | Biology, Molecular | en_US |
dc.subject | Biology, Genetics | en_US |
dc.title | Characterization of two transgene-induced mutations of the mouse: Sl(tg) and Del(19)TgN8052. | en_US |
dc.type | Thesis | en_US |
dc.description.thesisdegreename | PhD | en_US |
dc.description.thesisdegreediscipline | Cellular and Molecular Biology | en_US |
dc.description.thesisdegreegrantor | University of Michigan, Horace H. Rackham School of Graduate Studies | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/103970/1/9423226.pdf | |
dc.description.filedescription | Description of 9423226.pdf : Restricted to UM users only. | en_US |
dc.owningcollname | Dissertations and Theses (Ph.D. and Master's) |
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