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Rodent Autosomal Dominant Polycystic Kidney Disease Models
Published in Jinghua Hu, Yong Yu, Polycystic Kidney Disease, 2019
Sara J. Holditch, Raphael A. Nemenoff, Katharina Hopp
Collectively, these examples illustrate the importance of keeping precise records on genetic background, generation of inbreeding, and back-crossing experiments in order to be able to tease apart the phenotypic/mechanistic consequences unique to the gene of interest versus potential strain associated modifier gene/loci. This becomes especially important when generating double and triple genetically engineered rodent models across different background strains. Interestingly, murine models with dissimilar PKD-associated phenotypes across backgrounds would provide the perfect platform to identify potential modifier genes relevant to human ADPKD where large intra-/interfamilial phenotypic heterogeneity is observed. Such studies, while extremely tedious, have been performed by outcrossing inbred rodent models to a divergent strain and performing whole-genome genetic comparisons, also known as QTL mapping, among animals showing different grades of disease severity. In the case of PKD, this has been done for the kat2J, bpk, pcy, and Han-SPRD-cy models and suggests that genes such as Invs, Bicc1, Col4a3, or Slc21a2 may modify PKD severity.9,201,202,207,208
Gene Targeting Models of Epilepsy: Technical and Analytical Considerations
Published in Steven L. Peterson, Timothy E. Albertson, Neuropharmacology Methods in Epilepsy Research, 2019
Alternatively, many investigators seek to minimize genetic heterogeneity by backcrossing their hybrid mice to another inbred strain. Although such a breeding program can greatly reduce genetic variability, it has been recently pointed out that backcrossing will not readily eliminate 129-derived genes that are tightly linked to the target locus.46 For example, even after 12 generations of backcrossing to a C57BL/6 background, animals may retain a length of flanking 129-derived genetic material capable of encoding 300 genes. This could complicate data interpretation if significant differences in the relevant phenotype occur between C57BL/6 and 129 animals. Strategies to control for these effects include the use of transgenic approaches to rescue the mutant phenotype by restoring the targeted gene and the use of controls generated by crossing the wild-type progeny of chimeras.47 An optimal solution to these problems may lie in the ability to derive ES cell lines from other inbred strains, such as the well-characterized C57BL/6 strain.48 Chimeras generated from C57BL/6 ES cells could be crossed with C57BL/6 mice to yield null mutant and control animals devoid of genetic polymorphisms.
Norman Ernest Borlaug (1914–2009), M.S. Swaminathan (1925–), and Green Revolution
Published in Krishna Dronamraju, A Century of Geneticists, 2018
In 1953, Borlaug extended this technique by suggesting that several pure lines with different resistance genes should be developed through backcross methods using one recurrent parent. Backcrossing involves crossing a hybrid and subsequent generations with a recurrent parent. As a result, the genotype of the backcrossed progeny becomes increasingly similar to that of the recurrent parent. Borlaug’s method would allow the various different disease-resistant genes from several donor parents to be transferred into a single recurrent parent. To make sure each line has different resistant genes, each donor parent is used in a separate backcross program. Between 5 and 10 of these lines may then be mixed depending upon the races of pathogen present in the region. As this process is repeated, some lines will become susceptible to the pathogen. However, these lines can easily be replaced with new resistant lines.
Tbc1d10c is a selective, constitutive suppressor of the CD8 T-cell anti-tumor response
Published in OncoImmunology, 2022
Adrienne O. Cohen, Seung-Hyun Woo, Junya Zhang, Jiyoon Cho, Marlon E. Ruiz, Jianli Gong, Rong Du, Olga Yarygina, Danya Z. Jafri, Michael A. Bachelor, Michael O. Finlayson, Rajesh K. Soni, Matthew S. Hayden, David M. Owens
The targeting cassettes for Tbc1d10c null (Tbc1d10c−/−) and Tbc1d10c-CreERT2 transgenic mice were generated in our laboratory by bacterial artificial chromosome (BAC) recombineering approaches,32 and chimeric and transgenic founder mice were generated by the CUIMC Transgenic Mouse Core Facility (Supplemental Figures S1 and S2). Experimental Tbc1d10c−/− and Tbc1d10c+/+ (wild-type) mice were generated by backcrossing ten generations onto C57Bl/6 and FVB genetic backgrounds. Tbc1d10c-CreERT2 mice, backcrossed ten generations onto a FVB background, were crossed with FVB-backcrossed Rosa26mT/mG mice33 (Jackson Laboratories) to generate Tbc1d10c-CreERT2;Rosa26mT/mG bigenic mice. Rag2−/−,34OT-I transgenic,35 and OT-II transgenic36 mice were acquired from Jackson Laboratories. OT-I and OT-II transgenic mice were crossed to Tbc1d10c−/− mice to generate OT-I;Tbc1d10c−/− and OT-II;Tbc1d10c−/− lines. Rag2−/− mice were crossed to Tbc1d10c−/− mice to generate Rag2−/−;Tbc1d10c−/− double null mice. All animal housing and experiments were conducted under an approved Institutional Animal Care and Use Committee protocol (Protocol number AC-AABC3509).
The Drosophila melanogaster foraging gene affects social networks
Published in Journal of Neurogenetics, 2021
Nawar Alwash, Aaron M. Allen, Marla B. Sokolowski, Joel D. Levine
We sought to disentangle the social behavior and network effects that were attributed to the for gene from effects of genetic background. To this end, we used a line called R1 which has the rover for allele backcrossed (9x’s) into a sitter genetic background. This was accomplished by conducting two, nine generation backcrosses. In the first, null for mutants were backcrossed to the sitter strain for nine generations. In the second, the resulting line was used as a sitter background donor for an allele swap that put a rover allele into a sitter genetic background using another 9 generations of backcrossing. Since the for null mutant background donor had no for sequence, recombination of the rover allele could not occur at the for locus during these crosses. Thus, we used the for the null mutation to introgress the rover for locus into a sitter genetic background to generate the R1 strain.
Comparative Expression Analysis of Stress-Inducible Genes in Murine Immune Cells
Published in Immunological Investigations, 2020
Madoka Koyanagi, Yutaka Arimura
C57BL/6 and BALB/c mice were originally obtained from Japan SLC (Hamamatsu, Japan). GR congenic mice were generated as follows: C57BL/6 mice were crossed with BALB/c mice. To determine the GR genotype, we isolated genomic DNA from mouse-tails and performed PCR using the following GR primers: forward 5ʹ-CTG CTT CTC AGG CAG ATT CC-3ʹ and reverse 5ʹ-TCC AGA AGC CGA AAG TCT GT-3ʹ. The GR genes of C57BL/6 and BALB/c were amplified as 320 bp and 290 bp bands, respectively. C57BL/6 background GRBalb congenic mice were produced by backcrossing to C57BL/6 mice for at least 14 generations, in which more than 99.9% genome was assumed to be replaced (Markel et al. 1997). Heterozygous mice were intercrossed to produce GRBalb/Balb and GRB6/B6 homozygous GR congenic mice. BALB/c background GRB6 congenic mice were also generated in the same way. CRH KO mice were kindly provided by Dr. Majzoub (Muglia et al. 1995). All mice were bred in our animal facility, and 8-12-week-old mice were used for experiments. The animals were used in accordance with the guidelines of The Laboratory Animals Committee of Nippon Veterinary and Life Science University.