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1.
Linkage studies have identified many chromosomal regions containing obesity genes in mice. However, only a few of these quantitative trait loci (QTLs) have been used to guide the production of congenic mouse strains that retain obesity phenotypes. We seek to identify chromosomal regions containing obesity genes in the BSB model of spontaneous obesity because the BSB model is a multigenic obesity model. Previous studies identified QTLs on Chromosomes (Chrs) 2, 6, 7,12, and 15. BSB mice are made by backcross of lean C57BL/6J × Mus spretus. F1s were backcrossed to C57BL/6J mice to produce BSB progeny. We have constructed a new BSB cross and produced congenic mice with obesity phenotypes by marker-directed selection called B6.S–D2Mit194–D2Mit311. We found a highly significant QTL for percentage body lipid on Chr 2 just proximal to the Agouti locus. Chr 2 congenics were constructed to determine whether the main effects would be detectable. We observed highly significant linkage of the Chr 2 congenic containing Agouti and containing markers distal to D2Mit311 and proximal to D2Mit194. Thus, this congenic contains approximately 14.6 cM or 30 Mb (about 1.1% of the spretus mouse genome) and several hundred genes. The obesity phenotype of the QTL is retained in the congenic. The congenic can now be used to model the genetic and physiological basis for a relatively simple, perhaps monogenic, obesity. 相似文献
2.
Xia Li Masashi Inoue Danielle R. Reed Taufiqul Huque Ralph B. Puchalski Michael G. Tordoff Yuzo Ninomiya Gary K. Beauchamp Alexander A. Bachmanov 《Mammalian genome》2001,12(1):13-16
The Sac (saccharin preference) locus affecting mouse behavioral and neural responsiveness to sweeteners has been mapped to distal
Chr 4. A putative sweet taste receptor, T1R1, has been recently cloned, and the gene encoding it, Gpr70, has also been mapped to mouse distal Chr 4. To assess Gpr70 as a candidate gene for Sac, we compared the Gpr70 sequences of C57BL/6ByJ and 129P3/J mouse strains with different alleles of Sac. Using Gpr70 sequence variation between the C57BL/6ByJ and 129P3/J strains, we conducted a high-resolution analysis of the chromosomal
localization of the Gpr70 and Sac loci in the F2 hybrids and 129.B6-Sac partially congenic mice originating from these two strains. The Gpr70 gene maps proximal to Sac, which demonstrates that they are different loci.
Received: 24 April 2000 / Accepted: 14 September 2000 相似文献
3.
Q. Y. Zhang H. Dene A. Y. Deng M. R. Garrett H. J. Jacob J. P. Rapp 《Mammalian genome》1997,8(9):636-641
The renin locus (Ren) on rat Chromosome (Chr) 13 had previously been shown to cosegregate with blood pressure in crosses involving Dahl salt-sensitive
(S) and Dahl salt-resistant (R) rats. In the present work, interval mapping of blood pressure on Chr 13 with a large F2 (S × R), n = 233, population yielded a maximum LOD = 4.2 for linkage to blood pressure, but the quantitative trait locus
(QTL) was only poorly localized to a large 35-centiMorgan (cM) segment of Chr 13. In the linkage analysis, the S-rat QTL allele
(S) was associated with higher, and the R-rat QTL allele (R) with lower blood pressure, the difference between homozygotes being about 20 mm Hg. A congenic strain was made by introgressing
the R-rat Ren allele into the recipient S strain. This congenic strain showed a 24 mm Hg reduction (P = 0.004) in blood pressure compared
with S rats for rats fed 2% NaCl diet for 24 days; this difference was confirmed by two other independent tests. Two congenic
substrains were derived from the first congenic strain with shorter R Chr 13 segments on the S background. Comparisons among
these congenic strains showed that a blood pressure QTL was in the 24-cM chromosomal segment between Syt2 and D13M1Mit108. This segment does not include the renin locus, which is thus excluded from being the gene on rat Chr 13 responsible for genetic
differences in blood pressure detected by linkage analysis.
Received: 20 December 1996 / Accepted: 7 April 1997 相似文献
4.
Hall Richard J. Hollis-Moffatt Jade E. Merriman Marilyn E. Green Rachel A. Baker David Merriman Tony R. 《Mammalian genome》2003,14(5):335-339
Twenty-four named Idd loci that contribute to the development of autoimmune diabetes in the nonobese diabetic (NOD) mouse have been mapped by linkage and congenic analysis. Previously, meta-analysis of genome-wide linkage scans supported the existence of a locus for susceptibility to autoimmune phenotypes on rodent Chromosome (Chr) 18, in a position orthologous to the human type 1 diabetes susceptibility locus IDDM6 (human Chr 18q12-q23). However, an autoimmune diabetes susceptibility locus has not previously been reported on mouse Chr 18. In this study, we demonstrate linkage of the majority of mouse Chr 18 to diabetes in a (ABH × NOD)F1 × NOD backcross. Congenic analysis, introgressing at least 92% of Biozzi ABH Chr 18 onto the NOD background, confirmed the presence of a diabetes locus. The chromosome substitution strain (NOD.ABH-Chr18) had reduced diabetes incidence compared with NOD mice (P < 0.0001). We have named the Chr 18 diabetes locus Idd21. 相似文献
5.
Fanconi anemia (FA) is a chromosomal instability syndrome characterized by the presence of pancytopenia, congenital malformations and cancer predisposition. Six genes associated with this disorder have been cloned, and mice with targeted disruptions of several of the FA genes have been generated. These mouse models display the characteristic FA feature of cellular hypersensitivity to DNA cross-linking agents. Although they do not develop hematological or developmental abnormalities spontaneously, they mimic FA patients in their reduced fertility. Studies using these animal models provide valuable insights into the involvement of apoptotic pathways in FA, and help characterize the defects in FA hematopoietic cells. In addition, mouse models are also useful for testing treatments for FA. 相似文献
6.
Kenneth R. Johnson Sue A. Cook Patricia Ward-Bailey Michael Bustin Muriel T. Davisson 《Mammalian genome》1993,4(2):83-89
HMG-17 is an abundant, nonhistone chromosomal protein that binds preferentially to nucleosomal core particles of mammalian chromatin. The human gene for HMG-17 has been localized to Chromosome (Chr) 1p, but the murine gene has not been previously mapped. Here we identify the murine functional gene, Hmg17, from among more than 25 related sequences (probably processed pseudogenes) and show that it is located on mouse Chr 4, in a region known to have conserved linkage relationships with human Chr 1p. We also report the map locations of 20 additional Hmg17-related sequences on mouse Chrs 1, 2, 3, 5, 7, 8, 9, 13, 15, 16, 17, 18, and X. The multiple, dispersed members of the Hmg17 multigene family can be detected efficiently with a single cDNA probe and provide useful markers for genetic mapping studies in mice. 相似文献
7.
Saori Otsuka Yuka Namiki Osamu Ichii Yoshiharu Hashimoto Nobuya Sasaki Daiji Endoh Yasuhiro Kon 《Mammalian genome》2010,21(3-4):153-161
MRL/MpJ (MRL) mouse testes have several unique characteristics, including the appearance of oocytes, the occurrence of metaphase-specific apoptosis of meiotic spermatocytes, and the presence of heat-shock-resistant spermatocytes. In the present study we used chromosomal mapping to determine the genomic background associated with small testis size in MRL mice. We prepared and analyzed C57BL/6-based congenic mice carrying MRL mouse loci. Quantitative trait loci (QTL) analysis revealed susceptibility loci for small testis size at 100 cM on chromosome (Chr) 1 and at around 80 cM on Chr 2. Analysis with B6.MRLc1 and B6.MRLc2 congenic mice and double-congenic mice confirmed the QTL data and showed that low testis weight in MRL mice was caused by germ cell apoptosis. Through histological examinations we found that B6.MRLc1 and B6.MRLc2 mice showed stage-specific apoptosis in their testes, the former at metaphase stage XII and the later at pachytene stage IV. Metaphase-specific apoptosis of spermatocytes occurs due to mutation of the exonuclease 1 (Exo1) gene located at 100 cM on Chr 1. Thus, the mutation of the Exo1 gene is also responsible for low testis weight caused by metaphase-specific apoptosis. In conclusion, testis weight is reduced in MRL mice due to apoptosis of germ cells caused by mutations in loci on Chrs 1 and 2. 相似文献
8.
9.
Barbara York Alycia A. Truett Michelle P. Monteiro Sean J. Barry Craig H. Warden Jürgen K. Naggert Terry P. Maddatu David B. West 《Mammalian genome》1999,10(5):457-462
We have previously reported suggestive evidence for a locus on Chromosome (Chr) 7 that affects adiposity in F2 mice from a CAST/Ei × C57BL/6J intercross fed a high-fat diet. Here we characterize the effect of a high-fat (32.6 Kcal%
fat) diet on male and female congenic mice with a C57BL/6J background and a CAST/Ei-derived segment on Chr 7. Adiposity index
(AI) and weights of certain fat pads were approximately 50% lower in both male and female congenic mice than in control C57BL/6J
mice, and carcass fat content was significantly reduced. The reduction of fat depot weights was not seen, however, in congenic
animals fed a low-fat chow diet (12 Kcal% fat).
The congenic segment is approximately 25 cM in length, extending from D7Mit213 to D7Mit41, and includes the tub, Ucp2, and Ucp3, genes, all of which are candidate genes for this effect. Some polymorphisms have been found on comparing c-DNA sequences
of the Ucp2 gene from C57BL/6J and CAST/Ei mice. These results suggest that one or more genes present in the congenic segment modulate
the susceptibility to fat deposition on feeding a high-fat diet.
We were unable to show any significant difference between the energy intakes of the congenic and the control C57BL/6J mice
on the high-fat diet. Also, measurements of energy expenditure in male mice at 6 weeks of age, during the first 2 weeks of
exposure to the high-fat diet, failed to show any differences between control and congenic animals.
Received: 30 September 1998 / Accepted: 22 December 1998 相似文献
10.
Localization of Idd11 using NOD congenic mouse strains: elimination of Slc9a1 as a candidate gene 总被引:5,自引:0,他引:5
Type 1 diabetes is a multigenic autoimmune disease, the genetic basis for which is perhaps best characterized in the nonobese
diabetic (NOD) mouse model. We previously located a NOD diabetes susceptibility locus, designated Idd11, on mouse Chromosome (Chr) 4 by analyzing diabetic backcross mice produced after crossing NOD/Lt with the nondiabetic resistant strain C57BL/6 (B6) strain. In order to confirm Idd11 and further refine its location, three NOD congenic mouse strains with different B6 derived intervals within Chr 4 were generated.
Two of the congenic strains had a significant decrease in the cumulative incidence of diabetes compared with NOD/Lt control
mice. The third NOD congenic strain, containing a B6 interval surrounding the Slc9a1 locus, was not protected against diabetes. These results define a new distal boundary for Idd11 and eliminate the Slc9a1 gene as a candidate. The Idd11 locus has now been definitively mapped to a 13cM interval on mouse Chr 4.
Received: 15 May 1999 / Revised: 25 September 1999 相似文献
11.
A novel mouse gene, provisionally named Lx1, has been cloned and sequenced. Lx1 most likely represents the mouse homolog of the rat gene OCT1, which encodes a polyspecific transmembrane transporter that is possibly involved in drug elimination. The LX1 predicted protein
is highly hydrophobic, possesses twelve putative transmembrane domains, and also shares significant homology with members
of the sugar transporter family, particularly the novel liver-specific transporter NLT. Lx1 mRNA is expressed at high levels in mouse liver, kidney, and intestine, and at low levels in the adrenals and in lactating
mammary glands. The Lx1 gene maps very close to the imprinted Igf2r/Mpr300 gene on mouse Chromosome (Chr) 17, in a region that is syntenic to human Chr 6q. Chr 6q has been previously associated with
transient neonatal diabetes mellitus and breast cancer.
Received: 11 March 1996 / Accepted: 5 June 1996 相似文献
12.
J. Michael Salbaum 《Mammalian genome》1999,10(2):107-111
The mouse gene Punc encodes a member of the immunoglobulin superfamily of cell surface proteins. It is highly expressed in the developing embryo
in nervous system and limb buds. At mid-gestation, however, expression levels of Punc decrease sharply. To allow investigation of such a regulatory mechanism, the genomic locus encompassing the Punc gene was cloned, characterized, and mapped. Fluorescent in situ hybridization was used to determine the chromosomal location
of the Punc gene of mouse and human. Mouse Punc maps to Chromosome (Chr) 9 in the region D-E1, whereas the human PUNC gene is localized to Chr 15 at 15q22.3-23, a region
known to be syntenic to mouse 9D-E1. The human PUNC gene therefore maps close to a genetic locus that is linked to Bardet-Biedl
Syndrome, an autosomal recessive human disorder. Confirmation for the location of human PUNC was obtained through sequence
relationships between mouse Punc cDNA, human PUNC cDNA, genomic sequence upstream of the murine Punc gene, and human STS markers that had been previously mapped on Chr 15. The STS sequence WI-14920 is in fact derived from
the 3′-untranslated region of the human PUNC gene. WI-14920 had been placed at 228cR from the top of the Chr 15 linkage group,
which provided positional information for the human PUNC gene at high resolution. Thus, this study identifies PUNC as the
gene corresponding to a previously anonymous marker and serves as a basis to investigate its role in genetic disorders.
Received: 8 July 1998 / Accepted: 14 October 1998 相似文献
13.
Vijaya Ramesh Shirley V. Cheng Christine A. Kozak Bruce J. Herron Vivian E. Shih Benjamin A. Taylor James F. Gusella 《Mammalian genome》1992,3(1):17-22
Ornithine aminotransferase (OAT), a mitochondrial matrix enzyme, is deficient in patients with gyrate atrophy of the choroid and retina. In human, the OAT structural gene maps to Chromosome (Chr) 10q26 and several OAT-related sequences, some of which are known to be processed pseudogenes, which map to Xp11.3–11.21. Here, we report chromosomal localization in the mouse of the OAT gene and related sequences. Genomic DNA blot analysis of a well-characterized panel of Chinese hamster x mouse somatic cell hybrids using a human OAT probe revealed two murine loci, one on mouse Chr 7 and the other on Chr X. In addition, segregation of restriction fragment length polymorphisms (RFLPs) detected by the OAT probe in recombinant inbred (RI) strains detected a third locus on Chr 3 and positioned the X locus near Cf-8 and Rsvp. Progeny of an intersubspecific backcross were used to map the Chr 7 locus between Tyr and Int-2, near Cyp2e-1. 相似文献
14.
Géraldine Piessevaux Virginie Lella Michèle Rivière Daniel Stieber Pierre Drèze Josiane Szpirer Claude Szpirer 《Mammalian genome》2009,20(1):43-52
We previously defined quantitative trait loci (QTLs) that control susceptibility to 7,12-dimethylbenz(α)anthracene-induced
mammary carcinoma in SPRD-Cu3 (susceptible) and WKY (resistant) rats. Two of these QTLs, assigned to chromosomes (Chr) 10
and 18, control tumor growth rate and invasiveness. In this study we characterized a congenic strain in which a large segment
of WKY Chr 10 was introduced in the SPRD-Cu3 genetic background and demonstrated that this chromosome segment controls this
tumor trait. The WKY allele at this QTL (Mcsta1) reduces the growth rate of the fastest growing tumors by 26%. We also previously showed that two SPRD-Cu3-WKY congenic strains
containing a WKY chromosome segment derived either from Chr 5 or from Chr 18 exhibit a reduction in tumor multiplicity (QTLs
Msctm1 and Mcstm2, respectively) (with no reduction in tumor growth rate in the Chr 18 congenic). In this study we generated a double congenic
strain, which contains the two WKY differential segments from Chr 5 and 18, to determine how these two segments interact with
one another. Interestingly, two types of epistatic interactions were found: no additive effect was seen with respect to tumor
multiplicity, while a reduction in tumor growth rate was observed. It thus appears that WKY alleles located on Chr 5 and Chr
8 interact epistatically in a contrasting manner to modulate tumor multiplicity (in a nonadditive manner) and growth rate
(in a synergic manner). Tumor growth rate is thus influenced by two QTLs, on Chr 10 (Mcsta1) and on Chr 18 (Mcsta2), the action of the latter being dependent on the presence of the Chr5 QTL (Mcstm1). The expression level of positional and functional candidate genes was also analyzed. On Chr 5, Pla2g2a is subject to a syntenic control while expression of the Tp53 (Chr 10) and Pmai1/Noxa (Chr 18) genes appears to be controlled by several mammary cancer resistance QTLs. 相似文献
15.
Black rats are of outstanding interest in parasitology and infective disease analysis. We used chromosome paints from both
the mouse(Mus musculus) and the Norway rat(Rattus norvegicus) to characterize the genome of two Black rat subspecies from Italy. Both subspecies have two large metacentrics (n. 1, 4)
not present in the Norway rat (2n = 42).Rattus rattus rattus has a diploid number of 2n = 38, whileRattus rattus frugivorous has two small metacentric “supernumerary” or B chromosomes for a diploid number of 2n = 38 + 2B. The 21 mouse paints gave
38 signals on theR. r. rattus karyotype and 39 signals in theR. r. frugivorous karyotype. The two metacentrics, not present inR. norvegicus, were hybridized by mouse 16/1/17 and mouse 4/10/15. These chromosomes are homologous to: RRA1 = RNO 5/7, and RRA4 = RNO
9/11 and not “4/7” and “11/12” as previously reported. Furthermore, the synteny of Chr 13 of theR. r. frugivorous withR. norvegicus Chr 16 and mouse Chrs 8/14 is not complete, because there is a small pericentromeric insertion of RNO Chr 18 (mouse Chr 18).
If we consider only the two metacentrics, RRA1 and RRA4, the principal differences betweenR. norvegicus andR. rattus, then we can propose the derived synteny of 124 genes in the black rat. A comparison of the Z index between rats and mice
shows an acceleration of genomic evolution among genus, species, and subspecies. The chromosomal differences betweenR. r. rattus xR. r. frugivorous suggest that they may be classified as different species because hybrids would produce 50% unbalanced gametes. 相似文献
16.
Craig H. Warden Steven Stone Sally Chiu Adam L. Diament Pablo Corva Donna Shattuck Robyn Riley Steven C. Hunt Juliet Easlick Janis S. Fisler Juan F. Medrano 《Mammalian genome》2004,15(6):460-471
Our primary objective was to discover simplified mouse models corresponding to human obesity linkages. We used the B10.UW– H3b we Pax1un at/Sn (B10.UW) congenic strain, a subcongenic strain with a reduced UW strain donor region, and their C57BL/10SnJ background strain. The congenic and subcongenic UW strain donor regions are on mouse Chr 2. We measured body length [anal-nasal (AN) length], summed fat depot weights normalized for body weight (Adiposity Index, AI), and percentage of body weight that is lipid. The B10.UW congenic and subcongenic strains have significantly smaller AN lengths (p < 0.0001) and have a significantly lower AI and percentage of body weight as fat than the background strain (p < 0.0001). In an F2 intercross of the congenic and background strains, AN and AI were both linked to the distal half of the donor region with LOD scores greater than 19 and 5, respectively. F2 haplotypes identified a minimal region for AN linkage of 0.8 megabases (Mb) that is estimated to express four genes in the current Celera mouse genome assembly. We narrowed the most likely location of the obesity gene to 15 Mb whose homologous genes are all located on human Chr 20 in the region surrounding the centromere. Since a previous study identified human obesity linkage peaking near the centromere, then the B10.UW mice may exhibit obesity due to the homologous gene. 相似文献
17.
Genetic control of homeostasis of peripheral CD4+ lymphocyte levels is incompletely understood. Recent genome scans have linked mouse peripheral CD4 levels to chromosome 17, with strongest linkage to the Ea region. Nonobese diabetic (NOD) mice demonstrate peripheral T-cell lymphocytosis, and previous studies also suggested that the MHC region might control this phenotype. Here we confirm that loci on Chr 17 control NOD peripheral CD4 lymphocytosis. An elevated NOD CD4:CD8 ratio maps to the same region, and we show it is due to increased numbers of CD4+ cells. However, using NOD MHC congenic mice, we demonstrate that the MHC region is excluded, and that NOD peripheral lymphocytosis is controlled by genetic intervals adjacent to the MHC region on Chr 17. 相似文献
18.
M. Haas D. C. Ward J. Lee A. D. Roses V. Clarke P. D'Eustachio D. Lau E. Vega-Saenz de Miera B. Rudy 《Mammalian genome》1993,4(12):711-715
Four related genes, Shaker, Shab, Shaw, and Shal, encode voltage-gated K+ channels in Drosophila. Multigene subfamilies corresponding to each of these Drosophila genes have been identified in rodents and primates; this suggests that the four genes are older than the common ancestor of present-day insects and mammals and that the expansion of each into a family occurred before the divergence of rodents and primates.In order to define these evolutionary relationships more precisely and to facilitate the search for mammalian candidate K+ channel gene mutations, we have mapped members of the Shaw-homologous gene family in humans and mice. Fluorescence in situ hybridization analysis of human metaphase chromosomes mapped KCNC2 (KShIIIA, KV3.2) and KCNC3 (KShIIID, KV3.3) to Chromosome (Chr) 19q13.3-q13.4. Inheritance patterns of DNA restriction fragment length variants in recombinant inbred strains of mice placed the homologous mouse genes on distal Chr 10 near Ms15-8 and Mdm-1. The mouse Kcnc1 (KShIIIB, NGK2-KV4, KV3.1) gene mapped to Chr 7 near Tam-1.These results are consistent with the hypothesis that the generation of the mammalian KCNC gene family included both duplication events to generate family members in tandem arrays (KCNC2, KCNC3) and dispersion of family members to unlinked chromosomal sites (KCNC1). The KNCN2 and KCNC3 genes define a new synteny group between humans and mice. 相似文献
19.
Tsutomu Koizumi Marcy MacDonald Maja Búcan John J. Hopwood C. Phillip Morris Hamish S. Scott James F. Gusella Joseph H. Nadeau 《Mammalian genome》1992,3(1):23-27
-L-iduronidase (IDUA), which when deficient causes mucopolysaccharidosis type I, is located near the Huntington disease locus (HD) on human Chromosome (Chr) 4p16.3, approximately 106 base pairs (bp) from the telomere. As part of our continuing efforts to define a detailed comparative map for this chromosomal segment in mice and humans, we have used an interspecific backcross between C57BL/6J and an inbred strain derived from Mus spretus to map Idua, the mouse homolog of IDUA. We also mapped the mouse homolog of D4S115, an anonymous locus approximately 250 kb proximal to IDUA. As expected, both Idua and D4S115h are located on the proximal portion of mouse Chr5 near homologs for other loci on human Chr 4p. Comparison of gene order in mice and humans demonstrates, however, that a chromosomal rearrangement within this conserved synteny has occurred since divergence of lineages leading to mice and humans. 相似文献
20.
T. Agui T. Miyamoto C.-G. Jung T. Tsumagari K. Masuda T. Manabe 《Mammalian genome》2000,11(10):862-865
The LEC rat has been reported to exhibit X-ray hypersensitivity and deficiency in DNA double-strand break (DSB) repair. The
present study was performed to map the locus responsible for this phenotype, the xhs (X-ray hypersensitivity), as the first step in identifying the responsible gene. Analysis of the progeny of (BN × LEC)F1× LEC backcrosses indicated that the X-ray hypersensitive phenotype was controlled by multiple genetic loci in contrast to
the results reported previously. Quantitative trait loci (QTL) linkage analysis revealed two responsible loci located on Chromosomes
(Chr) 4 and 1. QTL on Chr 4 exhibited very strong linkage to the X-ray hypersensitive phenotype, while QTL on Chr 1 showed
weak linkage. The Rad52 locus, mutation of which results in hypersensitivity to ionizing radiation and impairment of DNA DSB repair in yeast, was
reported to be located on the synteneic regions of mouse Chr 6 and human Chr 12. However, mapping of the rat Rad52 locus indicated that it was located 23 cM distal to the QTL on Chr 4. Furthermore, none of the radio-sensitivity-related
loci mapped previously in the rat chromosome were identical to the QTL on Chrs 4 and 1 in the LEC rat. Thus, it seems that
X-ray hypersensitivity in the LEC rat is caused by mutation(s) in as-yet-undefined genes.
Received: 14 February 2000 / Accepted: 17 May 2000 相似文献