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{"title"=>"Postnatal survival of mice with maternal duplication of distal chromosome 7 induced by a Igf2/H19 imprinting control region lacking insulator function", "type"=>"journal", "authors"=>[{"first_name"=>"Li", "last_name"=>"Han", "scopus_author_id"=>"57188551493"}, {"first_name"=>"Piroska E.", "last_name"=>"Szabó", "scopus_author_id"=>"55392250600"}, {"first_name"=>"Jeffrey R.", "last_name"=>"Mann", "scopus_author_id"=>"7402727397"}], "year"=>2010, "source"=>"PLoS Genetics", "identifiers"=>{"pmid"=>"20062522", "isbn"=>"1553-7404 (Electronic)\r1553-7390 (Linking)", "doi"=>"10.1371/journal.pgen.1000803", "issn"=>"15537390", "scopus"=>"2-s2.0-76749105260", "pui"=>"358308141", "sgr"=>"76749105260"}, "id"=>"e460480b-c832-33c2-bc89-7c6a4ef20949", "abstract"=>"The misexpressed imprinted genes causing developmental failure of mouse parthenogenones are poorly defined. To obtain further insight, we investigated misexpressions that could cause the pronounced growth deficiency and death of fetuses with maternal duplication of distal chromosome (Chr) 7 (MatDup.dist7). Their small size could involve inactivity of Igf2, encoding a growth factor, with some contribution by over-expression of Cdkn1c, encoding a negative growth regulator. Mice lacking Igf2 expression are usually viable, and MatDup.dist7 death has been attributed to the misexpression of Cdkn1c or other imprinted genes. To examine the role of misexpressions determined by two maternal copies of the Igf2/H19 imprinting control region (ICR)-a chromatin insulator, we introduced a mutant ICR (ICR(Delta)) into MatDup.dist7 fetuses. This activated Igf2, with correction of H19 expression and other imprinted transcripts expected. Substantial growth enhancement and full postnatal viability was obtained, demonstrating that the aberrant MatDup.dist7 phenotype is highly dependent on the presence of two unmethylated maternal Igf2/H19 ICRs. Activation of Igf2 is likely the predominant correction that rescued growth and viability. Further experiments involved the introduction of a null allele of Cdkn1c to alleviate its over-expression. Results were not consistent with the possibility that this misexpression alone, or in combination with Igf2 inactivity, mediates MatDup.dist7 death. Rather, a network of misexpressions derived from dist7 is probably involved. Our results are consistent with the idea that reduced expression of IGF2 plays a role in the aetiology of the human imprinting-related growth-deficit disorder, Silver-Russell syndrome.", "link"=>"http://www.mendeley.com/research/postnatal-survival-mice-maternal-duplication-distal-chromosome-7-induced-igf2h19-imprinting-control", "reader_count"=>18, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>9, "Other"=>1, "Student > Master"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>9, "Other"=>1, "Student > Master"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>10, "Medicine and Dentistry"=>3, "Neuroscience"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}}, "reader_count_by_country"=>{"Netherlands"=>1, "India"=>1}, "group_count"=>2}

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• http://doi.org/10.1242/dmm.044123
• http://doi.org/10.1002/stem.1726
• http://doi.org/10.2217/epi-2016-0073
• http://doi.org/10.1128/MCB.00961-10
• http://doi.org/10.1534/genetics.110.118802
• http://doi.org/10.1139/o10-111
• http://doi.org/10.1093/bfgp/elq010
• http://doi.org/10.3390/cells9040993
• http://doi.org/10.1371/journal.pone.0012630

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• {"files"=>["https://ndownloader.figshare.com/files/868650"], "description"=>"<p>(A) Weight gain in litter matched MatDup.dist7 (ICR^Δ.+, <i>Cdkn1c</i>^+.+) or (ICR^Δ.Δ, <i>Cdkn1c</i>^+.+) young obtained from matings of (T9H/+, <i>Tyr^c</i>^/<i>c</i>, ICR^Δ/+ ♀×T9H/+, Tyr^+/+, ICR^+/+ ♂) and (T9H/+, <i>Tyr^c</i>^/<i>c</i>, ICR^Δ/+, <i>Cdkn1c</i>^+/− ♀×T9H/+, <i>Tyr</i>^+/+, ICR^+/+, <i>Cdkn1c</i>^+/+ ♂) mice. Each graph represents a single litter where at least one control with the same number of active <i>Igf2</i> alleles was obtained. Each bar represents a single animal. The paired-sample <i>t</i>-test was used to determine the probability that the weight of MatDup.dist7 and control mice was equal. For three-animal litters, the pairs used in the statistical test are indicated by the bracket above the bars. The <i>P</i> value was <0.01 for 6 week old mice, indicating a significant difference, while there was no significant difference in weight at 1, 2, and 3 weeks of age. (B) All weight gain data collected from the two sets of matings as described in (A) regardless of littermate matching. Bars are mean±s.d., with (n) given above the 1 wk bars. The two-sample <i>t</i>-test was used to determine the probability that two 6 week samples (identified as paired squares) were equal. Key: alleles are maternal.maternal in derivation for MatDup.dist7 and maternal/paternal in derivation for controls.</p>", "links"=>[], "tags"=>["post-partum", "mice", "rescued"], "article_id"=>539114, "categories"=>["Developmental Biology", "Genetics", "Evolutionary Biology"], "users"=>["Li Han", "Piroska E. Szabo", "Jeffrey R. Mann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000803.g005", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Weight_gain_in_post_partum_MatDup_dist7_mice_rescued_by_ICR_916_/539114", "title"=>"Weight gain in post-partum MatDup.dist7 mice rescued by ICR^Δ.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 03:11:06"}
• {"files"=>["https://ndownloader.figshare.com/files/868391"], "description"=>"<p>(A) Quadrivalents at meiosis I occurring in (T9H/+, <i>Tyr^c</i>^/<i>c</i>, ICR^Δ/+ ♀×T9H/+, <i>Tyr</i>^+/+, ICR^+/+ ♂) matings. Female reciprocal translocation heterozygote (T9H/+) parent is homozygous for the dist7 marker albino (<i>Tyr^c</i>^/<i>c</i>) and carries ICR^Δ (ICR^Δ/+), while the male T9H/+ parent is wild-type at both of these loci (<i>Tyr</i>^+/+, ICR^+/+). (B) Genotypes of MatDup.dist7 fetuses obtained from the union of unbalanced complementary gametes. MatDup.dist7 individuals are readily identified as albinos from 12½ dpc by lack of eye or fur pigmentation. Many of these are ICR^Δ.+ although a high frequency of homozygous recombinants, ICR^Δ.Δ and ICR^+.+, are also obtained. Chrs depicted are actually paired chromatids. Underneath is depicted allele-specific expression—MatDup.dist7 ICR^Δ.+ and ICR^Δ.Δ fetuses have one and probably two activated <i>Igf2</i> alleles, and should have one and two repressed <i>H19</i> alleles, respectively.</p>", "links"=>[], "tags"=>["developmental biology/developmental evolution", "developmental biology/developmental molecular mechanisms", "evolutionary biology/developmental evolution", "genetics and genomics/epigenetics", "genetics and genomics/gene expression"], "article_id"=>538846, "categories"=>["Developmental Biology", "Genetics", "Evolutionary Biology"], "users"=>["Li Han", "Piroska E. Szabo", "Jeffrey R. Mann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000803.g002", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Production_of_MatDup_dist7_fetuses_/538846", "title"=>"Production of MatDup.dist7 fetuses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 03:09:37"}
• {"files"=>["https://ndownloader.figshare.com/files/868467"], "description"=>"<p>(A) Northern blots for the imprinted genes <i>Igf2</i> and <i>Cdkn1c</i>, and for the housekeeping <i>Gapdh</i> gene for normalization. Each lane is an individual fetus. ICR genotype is given immediately above the lanes. (B) Northern blots in (A) were quantitated to show relative RNA levels. Values for <i>Igf2</i> and <i>Cdkn1c</i> were normalized to <i>Gapdh</i> RNA, calibrated to control ICR^+/+ values, and adjusted to a mean of 1.0. Values are mean±s.d. with (n) as shown in (A). Mating scheme to breed these animals was as described in the legend to <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000803#pgen-1000803-g002\" target=\"_blank\">Figure 2</a>.</p>", "links"=>[], "tags"=>["imprinted", "genes", "dpc"], "article_id"=>538926, "categories"=>["Developmental Biology", "Genetics", "Evolutionary Biology"], "users"=>["Li Han", "Piroska E. Szabo", "Jeffrey R. Mann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000803.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_imprinted_genes_in_13_189_dpc_MatDup_dist7_fetuses_/538926", "title"=>"Expression of imprinted genes in 13½ dpc MatDup.dist7 fetuses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 03:10:05"}
• {"files"=>["https://ndownloader.figshare.com/files/868550"], "description"=>"<p>MatDup.dist7 (ICR^Δ.+, <i>Cdkn1c</i>^+.+) albino neonate with two agouti littermates at 10 days post-partum. Mating scheme to breed these animals was as described in the legend to <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000803#pgen-1000803-g002\" target=\"_blank\">Figure 2</a>.</p>", "links"=>[], "tags"=>["rescued"], "article_id"=>539014, "categories"=>["Developmental Biology", "Genetics", "Evolutionary Biology"], "users"=>["Li Han", "Piroska E. Szabo", "Jeffrey R. Mann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000803.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Neonatal_MatDup_dist7_mouse_rescued_by_ICR_916_/539014", "title"=>"Neonatal MatDup.dist7 mouse rescued by ICR^Δ.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 03:10:37"}
• {"files"=>["https://ndownloader.figshare.com/files/868318"], "description"=>"<p>Young were obtained from (ICR^Δ/+, <i>Igf2</i>^+/+ ♀×ICR^+/+, <i>Igf2</i>^+/− ♂) matings. Bars are mean±s.d., with (n) given above the 1 wk bars. Key: alleles are maternal/paternal in derivation. The two-sample <i>t</i>-test was used to determine the probability that two 6 week samples (identified as paired squares) were equal.</p>", "links"=>[], "tags"=>["mutants", "carrying"], "article_id"=>538775, "categories"=>["Developmental Biology", "Genetics", "Evolutionary Biology"], "users"=>["Li Han", "Piroska E. Szabo", "Jeffrey R. Mann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000803.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Weight_gain_in_Igf2_mutants_carrying_ICR_916_/538775", "title"=>"Weight gain in <i>Igf2</i> mutants carrying ICR^Δ.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 03:09:10"}

PMC Usage Stats | Further Information

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Relative Metric

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F1000Prime