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1.
Price SJ Chittenden LR Flaherty L O'Dell B Guay-Woodford LM Stubbs L Bryda EC 《Cytogenetic and genome research》2002,98(1):61-66
The jcpk gene on mouse Chromosome 10 causes a severe, early onset form of polycystic kidney disease (PKD) when inherited in an autosomal recessive manner. In order to positionally clone this gene, high resolution genetic and radiation hybrid maps were generated along with a detailed physical map of the approximately 500-kb region containing the jcpk gene. Additionally, sixty-nine kidney-specific ESTs were evaluated as candidates for jcpk and subsequently localized throughout the mouse genome by radiation hybrid mapping analysis. Previous studies indicating non-complementation of the jcpk mutation and 67Gso, a new PKD translocation mutant had suggested that 67Gso represents a new allele of jcpk. Fluorescence in situ hybridization (FISH) analysis using key bacterial artificial chromosome clones from the jcpk critical region, refined the 67Gso breakpoint and provided support for the allelism of jcpk and 67Gso. 相似文献
2.
In the course of large-scale mutagenesis studies, we discovered a mutant that provides a new mouse model for human autosomal recessive polycystic kidney disease. Animals homozygous for this mutation, T(2;10)67Gso, present evidence of grossly cystic renal and hepatic tissue at birth and a limited survival time of 3-4 days. The recessively expressed phenotype is associated with inheritance of a reciprocal translocation involving mouse chromosomes 2 and 10. Here we describe the pathology and phenotype of this new mutation. The mapping of the chromosomal breakpoint to the 1.0-cM critical region defined for another mouse autosomal recessive polycystic kidney disease model, juvenile congenital polycystic kidney disease (jcpk), led us to undertake the complementation testing that confirmed T(2;10)67Gso and jcpk are allelic. Because of the strong resemblance between the phenotype associated with these mouse mutations and early childhood polycystic kidney disease, and because of advantages offered by reciprocal translocations for gene mapping and cloning, T(2;10)67Gso should prove a valuable asset for studies concerning this fatal disease. 相似文献
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The yeast homolog to mouse Tcp-1 affects microtubule-mediated processes. 总被引:23,自引:3,他引:20
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A Saccharomyces cerevisiae homolog to Drosophila melanogaster and mouse Tcp-1 encoding tailless complex polypeptide 1 (TCP1) has been identified, sequenced, and mapped. The mouse t complex has been under scrutiny for six decades because of its effects on embryogenesis and sperm differentiation and function. TCP1 is an essential gene in yeast cells and is located on chromosome 4R, linked to pet14. The TCP1-encoded proteins in yeast, Drosophila, and mouse cells share between 61 and 72% amino acid sequence identities, suggesting a primordial function for the TCP1 gene product. To assess function, we constructed a cold-impaired recessive mutation (tcp1-1) in the yeast gene. Cells carrying the tcp1-1 mutation grew linearly rather than exponentially at the restrictive temperature of 15 degrees C with a generation time of approximately 32 h in minimal medium. Both multinucleate and anucleate cells accumulated with time, suggesting that the linear growth kinetics may be explained by the generation of anucleate buds incapable of further cell division. In addition, the multinucleate and anucleate cells contained morphologically abnormal structures detected by anti-alpha-tubulin antibodies. The kinetics of appearance of these abnormalities suggest that they are a direct consequence of loss of function of the TCP1 protein and not a delayed, indirect consequence of cell death. We also observed that strains carrying tcp1-1 were hypersensitive to antimitotic compounds. Taken together, these observations imply that the TCP1 protein affects microtubule-mediated processes. 相似文献
5.
Bni1p implicated in cytoskeletal control is a putative target of Rho1p small GTP binding protein in Saccharomyces cerevisiae. 总被引:8,自引:3,他引:5
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H Kohno K Tanaka A Mino M Umikawa H Imamura T Fujiwara Y Fujita K Hotta H Qadota T Watanabe Y Ohya Y Takai 《The EMBO journal》1996,15(22):6060-6068
The RHO1 gene encodes a homolog of mammalian RhoA small GTP binding protein in the yeast Saccharomyces cerevisiae. Rho1p is localized at the growth sites, including the bud tip and the cytokinesis site, and is required for bud formation. We have recently shown that Pkc1p, a yeast homolog of mammalian protein kinase C, and glucan synthase are targets of Rho1p. Using the two-hybrid screening system, we cloned a gene encoding a protein which interacted with the GTP-bound form of Rho1p. This gene was identified as BNI1, known to be implicated in cytokinesis or establishment of cell polarity in S.cerevisiae. Bni1p shares homologous domains (FH1 and FH2 domains) with proteins involved in cytokinesis or establishment of cell polarity, including formin of mouse, capu and dia of Drosophila and FigA of Aspergillus. A temperature-sensitive mutation in which the RHO1 gene was replaced by the mammalian RhoA gene showed a synthetically lethal interaction with the bni1 mutation and the RhoA bni1 mutant accumulated cells with a deficiency in cytokinesis. Furthermore, this synthetic lethality was caused by the incapability of RhoA to activate Pkc1p, but not glucan synthase. These results suggest that Rho1p regulates cytoskeletal reorganization at least through Bni1p and Pkc1p. 相似文献
6.
Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C)
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Fan X Zhang H Zhang S Bagshaw RD Tropak MB Callahan JW Mahuran DJ 《American journal of human genetics》2006,79(4):738-744
Mucopolysaccharidosis IIIC (MPS IIIC), or Sanfilippo C, represents the only MPS disorder in which the responsible gene has not been identified; however, the gene has been localized to the pericentromeric region of chromosome 8. In an ongoing proteomics study of mouse lysosomal membrane proteins, we identified an unknown protein whose human homolog, TMEM76, was encoded by a gene that maps to 8p11.1. A full-length mouse expressed sequence tag was expressed in human MPS IIIC fibroblasts, and its protein product localized to the lysosome and corrected the enzymatic defect. The mouse sequence was used to identify the full-length human homolog (HGSNAT), which encodes a protein with no homology to other proteins of known function but is highly conserved among plants and bacteria. Mutational analyses of two MPS IIIC cell lines identified a splice-junction mutation that accounted for three mutant alleles, and a single base-pair insertion accounted for the fourth. 相似文献
7.
Hims MM Shetty RS Pickel J Mull J Leyne M Liu L Gusella JF Slaugenhaupt SA 《Genomics》2007,90(3):389-396
Familial dysautonomia (FD) is a severe hereditary sensory and autonomic neuropathy, and all patients with FD have a splice mutation in the IKBKAP gene. The FD splice mutation results in variable, tissue-specific skipping of exon 20 in IKBKAP mRNA, which leads to reduced IKAP protein levels. The development of therapies for FD will require suitable mouse models for preclinical studies. In this study, we report the generation and characterization of a mouse model carrying the complete human IKBKAP locus with the FD IVS20+6T-->C splice mutation. We show that the mutant IKBKAP transgene is misspliced in this model in a tissue-specific manner that replicates the pattern seen in FD patient tissues. Creation of this humanized mouse is the first step toward development of a complex phenotypic model of FD. These transgenic mice are an ideal model system for testing the effectiveness of therapeutic agents that target the missplicing defect. Last, these mice will permit direct studies of tissue-specific splicing and the identification of regulatory factors that play a role in complex gene expression. 相似文献
8.
The gene for retinal S-antigen (48-kDa protein) maps to the centromeric portion of mouse chromosome 1 near Idh-1 总被引:2,自引:0,他引:2
S-antigen (48-kDa protein) is a soluble protein of the retina and the pineal gland that is believed to play an important role in the visual process. S-antigen is involved in the regulation of the activity of rod photoreceptor-specific cGMP-phosphodiesterase (cGMP-PDE). The activity of this enzyme has been shown to be deficient in the retina of the rd mouse, which is affected by an autosomal recessive disease characterized by degeneration of the photoreceptor cells. The abnormal cGMP-PDE activity could result from, among other things, a lesion in the enzyme itself or in any of the proteins that regulate it, such as the S-antigen. We have used a mouse cDNA clone for the S-antigen to map the corresponding gene, Sag, to mouse chromosome 1 near Idh-1. Since the rd gene is located on mouse chromosome 5, our results suggest that Sag is not the site of the rd mutation. 相似文献
9.
Phenylketonuria (PKU) is an inborn error of amino acid metabolism. Phenylalanine hydroxylase (PAH) deficiency results in accumulation of phenylalanine (Phe) in the brain and leads to pathophysiological abnormalities including cognitive defect, if Phe diet is not restricted. Neuronatin and 4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) reportedly have role in memory. Therefore, gene expression was examined in the brain of mouse model for PKU. Microarray expression analysis revealed reduced expression of calpastatin, NIPSNAP 1, rabaptin-5 and minopontin genes and overexpression of neuronatin gene in the PKU mouse brain. Altered expression of these genes was further confirmed by one-step real time RT-PCR analysis. Western blot analysis of the mouse brain showed reduced levels of calpastatin and rabaptin-5 and higher amount of neuronatin in PKU compared to the wild type. These observations in the PKU mouse brain suggest that altered expression of these genes resulting in abnormal proteome. These changes in the PKU mouse brain are likely to contribute cognitive impairment seen in the PKU mouse, if documented also in patients with PKU. 相似文献
10.
Location of the gene involving the small eye mutation on mouse chromosome 2 suggests homology with human aniridia 2 (AN2) 总被引:3,自引:0,他引:3
R van der Meer-de Jong M E Dickinson R P Woychik L Stubbs C Hetherington B L Hogan 《Genomics》1990,7(2):270-275
Using an interspecific backcross, we have mapped the gene involved in the mouse Small eye mutation (SeyMH) relative to six cloned markers on chromosome 2 (Hox-5.1, Cas-1, Fshb, Bmp-2a, and ld) and the agouti locus. The results suggest that the Sey gene maps between Fshb and Cas-1. Human mapping studies have shown that the aniridia (AN2) gene, which is part of the Wilms tumor susceptibility, aniridia, genitourinary abnormalities, and mental retardation (WAGR) complex, is also between FSHB and CAT on human chromosome 11. The conserved linkage of the cloned markers and the similarity of the Sey/+ and AN2/+ phenotypes suggest that the gene involved in the Sey mutation is the mouse homolog of the human AN2 gene. 相似文献
11.
Interactions between homologs in meiotic prophase I, such as recombination and synapsis, are critical for proper homolog segregation and involve the coordination of several parallel events. However, few regulatory genes have been identified; in particular, it is not clear what roles the proteins similar to the mitotic cell cycle regulators might play during meiotic prophase I. We describe here the isolation and characterization of a new Arabidopsis mutant called solo dancers that exhibits a severe defect in homolog synapsis, recombination and bivalent formation in meiotic prophase I, subsequently resulting in seemingly random chromosome distribution and formation of abnormal meiotic products. We further demonstrate that the mutation affects a meiosis-specific gene encoding a novel protein of 578 amino acid residues with up to 31% amino acid sequence identity to known cyclins in the C-terminal portion. These results argue strongly that homolog interactions during meiotic prophase I require a novel meiosis-specific cyclin in Arabidopsis. 相似文献
12.
Cornier AS Staehling-Hampton K Delventhal KM Saga Y Caubet JF Sasaki N Ellard S Young E Ramirez N Carlo SE Torres J Emans JB Turnpenny PD Pourquié O 《American journal of human genetics》2008,82(6):1334-1341
Spondylothoracic dysostosis (STD), also known as Jarcho-Levin syndrome (JLS), is an autosomal-recessive disorder characterized by abnormal vertebral segmentation and defects affecting spine formation, with complete bilateral fusion of the ribs at the costovertebral junction producing a "crab-like" configuration of the thorax. The shortened spine and trunk can severely affect respiratory function during early childhood. The condition is prevalent in the Puerto Rican population, although it is a panethnic disorder. By sequencing a set of candidate genes involved in mouse segmentation, we identified a recessive E103X nonsense mutation in the mesoderm posterior 2 homolog (MESP2) gene in a patient, of Puerto Rican origin and from the Boston area, who had been diagnosed with STD/JLS. We then analyzed 12 Puerto Rican families with STD probands for the MESP2 E103X mutation. Ten patients were homozygous for the E103X mutation, three patients were compound heterozygous for a second nonsense mutation, E230X, or a missense mutation, L125V, which affects a conserved leucine residue within the bHLH region. Thus, all affected probands harbored the E103X mutation. Our findings suggest a founder-effect mutation in the MESP2 gene as a major cause of the classical Puerto Rican form of STD/JLS. 相似文献
13.
M Lovett D Goldgaber P Ashley D R Cox D C Gajdusek C J Epstein 《Biochemical and biophysical research communications》1987,144(2):1069-1075
The human amyloid beta protein is the major constituent of the brain amyloid plaques found in Alzheimer disease. The gene that encodes this protein is located on chromosome 21, and individuals with Down syndrome (trisomy 21) also exhibit an early onset form of Alzheimer disease. We have used the cloned human amyloid beta protein gene and a panel of somatic cell hybrids to map the location of the mouse homolog of this gene. We report here that the mouse gene is located on chromosome 16 within the region 16C3----ter, in common with three other genes which map within the Down syndrome region of human chromosome 21. 相似文献
14.
The nucleotide modification in tRNA plays a pivotal role in the fidelity of translational process. The defects in nucleotide modification have often been observed in the mutated mitochondrial tRNAs associated with human diseases. Recently, MTO1-like protein in bacteria and yeast has been implicated to be a component of tRNA modification pathway. Here we report the identification and characterization of mouse MTO1 homolog. The mouse MTO1 gene containing 12 exons encodes a 669-residue protein with a strong homology to the MTO1-like proteins of bacteria and yeast, related to tRNA modification. Functional conservation of this protein is supported by the observation that the isolated mouse MTO1 cDNA can complement the respiratory-deficient phenotype of yeast mto1 cells carrying P(R)(454) mutation. MTO1 is ubiquitously expressed in various tissues, but with markedly elevated expression in tissues of high metabolic rates. Furthermore, we showed that mouse Mto1 localizes in mitochondrion. These observations suggest that the mouse MTO1 is a structural and functional homolog of yeast MTO1, thereby playing a role in the mitochondrial tRNA modification and protein synthesis. 相似文献
15.
Assignment of the beta-subunit of rod photoreceptor cGMP phosphodiesterase gene PDEB (homolog of the mouse rd gene) to human chromosome 4p16. 总被引:2,自引:0,他引:2
J B Bateman I Klisak T Kojis T Mohandas R S Sparkes T S Li M L Applebury C Bowes D B Farber 《Genomics》1992,12(3):601-603
The gene encoding the beta-subunit of rod photoreceptor cGMP phosphodiesterase (gene symbol PDEB, homolog of the mouse rd gene) is mapped to human chromosome 4 using somatic cell hybrids and further localized to the chromosome band 4p16 using in situ hybridization. A mutation in the mouse gene underlies the recessive trait of retinal degeneration in the rd mouse. Thus, the human homolog is a candidate for lesions causing retinal degeneration. 相似文献
16.
A double missense mutation in the ATM gene of a Dutch family with ataxia telangiectasia 总被引:1,自引:0,他引:1
M. J. van Belzen Johan A. P. Hiel Corry M. R. Weemaes F. J. M. Gabreëls Baziel G. M. van Engelen Dominique F. C. M. Smeets L. P. W. J. van den Heuvel 《Human genetics》1998,102(2):187-191
Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectasia, immunodeficiency,
elevated α-fetoprotein levels, chromosomal instability, predisposition to cancer, and radiation sensitivity. We report the
identification of a new, double missense mutation in the ataxia telangiectasia gene (ATM) of a Dutch family. This homozygous
mutation consists of two consecutive base substitutions in exon 55: a T→G transversion at position 7875 of the ATM cDNA and
a G→C transversion at position 7876. These transversions were confirmed by polymerase chain reaction/primer-induced restriction
analysis with CelII. The double base substitution results in an amino acid change of an aspartic acid to a glutamic acid at codon 2625 and
of an alanine to a proline at codon 2626 of the ATM protein. Both amino acids are conserved between the ATM protein and its
functional homolog, the Atm gene product in the mouse. Furthermore, the Chou-Fasman and Robson predictions both demonstrate
a change in the secondary structure of the ATM protein carrying the D2625E/A2626P mutation. These findings suggest that the
double base substitution in the ATM gene is a disease-causing mutation.
Received: 6 October 1997 / Accepted: 5 November 1997 相似文献
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Characterization of cDNA encoding mouse homolog of fission yeast dhp1+ gene: structural and functional conservation. 总被引:3,自引:0,他引:3
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The dhp1+ gene of Schizosaccharomyces pombe is a homolog of Saccharomyces cerevisiae HKE1/RAT1/TAP1 gene that is involved in RNA metabolism such as RNA trafficking and RNA synthesis. dhp1+ is also related to S. cerevisiae DST2 (SEP1) that encodes a DNA strand exchange protein required for sporulation and homologous recombination in S.cerevisiae. We isolated several clones of Dhm1, a mouse homolog of dhp1+, from mouse spermatocyte cDNA library and determined its nucleotide sequence. The Dhm1 gene consists of an open reading frame predicting a protein with 947 amino acids and molecular weight of 107,955. Northern blot analysis revealed that Dhm1 is transcribed at high level in testis, liver and kidney. The predicted product of Dhm1 (Dhm1p) has a significant homology with Dhp1p, Hke1p/Rat1p/Tap1p and Dst2p. In particular, Dhm1p, Dhp1p and Hke1p/Rat1p/Tap1p share strong similarity at the two regions of their N- and C-terminal parts. The Dhm1 gene on a multicopy plasmid rescued the temperature-sensitivity of dhp1ts and lethality of dhp1 null mutation, suggesting that Dhm1 is a mouse homolog of S.pombe dhp1+ and functions similarly in mouse as dhp1+. 相似文献
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Lee JW Lee EJ Hong SH Chung WH Lee HT Lee TW Lee JR Kim HT Suh JG Kim TY Ryoo ZY 《Comparative medicine》2001,51(6):550-554
Mutant mice with abnormalities are potentially useful as models for studying human defects. Here we report a group of mice with abnormal behavioral patterns. A new spontaneous mutant mouse exhibited hyperactive behavior at about seven days of age, followed by tight circling behavior. Breeding studies suggest that this mutation is caused by a single gene defect inherited in an autosomal recessive manner. Consequently, this mutation is referred to as a circling (cir) mouse mutation with the gene symbol cir. Auditory test results identified clearly the hearing loss of the cir, compared with wild-type mice. Pathologic studies confirmed developmental defects in cochlea and spiral ganglions that were correlated to the abnormal behavior observed in the cir mice. Thus, cir mice may be useful as a model for studying inner ear abnormalities and deafness in humans. 相似文献