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At least 505 records · Page 28Linked to original sources
PubMed2005

Conservation of the E-function for floral organ identity in rice revealed by the analysis of tissue culture-induced loss-of-function mutants of the OsMADS1 gene.

Rapid progress in studies on flower development has resulted in refining the classical 'ABC model' into a new 'ABCDE model' to explain properly the regulation of floral organ identity. Conservation of E-function for flower organ identity among the dicotyledonous (dicot) plants has been revealed. However, its conservation in monocotyledonous (monocot) plants remains largely unknown. Here, we show the conservation of E-function in rice (Oryza sativaL.) by characterizing tissue culture-induced mutants of two MADS-box genes, OsMADS1and OsMADS5, which form a subclade within the well-supported clade of SEP-genes (E-function) phylogeny. Severe loss-of-function mutations of OsMADS1cause complete homeotic conversion of organs (lodicules, stamens, and carpels) of three inner whorls into lemma- and palea-like structures. Such basic deformed structure is reiterated along with the pedicel at the center of the same floret, indicating the loss of determinacy of the flower meristem. These phenotypes resemble the phenotypes caused by mutations of the dicot E-class genes, such as the Arabidopsis SEP123(SEPALLATA1/2/3) and the petunia FBP2(Floral Binding Protein 2), suggesting that OsMADS1play a very similar role in rice to that of defined E-class genes in dicot plants. In case of the loss-of-function mutation of OsMADS5, no defect in either panicles or vegetative organs was observed. These results demonstrate that OsMADS1clearly possesses E-function, and so, E-function is fundamentally conserved between dicot plants and rice, a monocot model plant.

Alleles↗
PubMed1999

A genetic screen for modifiers of E2F in Drosophila melanogaster.

The activity of the E2F transcription factor is regulated in part by pRB, the protein product of the retinoblastoma tumor suppressor gene. Studies of tumor cells show that the p16(ink4a)/cdk4/cyclin D/pRB pathway is mutated in most forms of cancer, suggesting that the deregulation of E2F, and hence the cell cycle, is a common event in tumorigenesis. Extragenic mutations that enhance or suppress E2F activity are likely to alter cell-cycle control and may play a role in tumorigenesis. We used an E2F overexpression phenotype in the Drosophila eye to screen for modifiers of E2F activity. Coexpression of dE2F and its heterodimeric partner dDP in the fly eye induces S phases and cell death. We isolated 33 enhancer mutations of this phenotype by EMS and X-ray mutagenesis and by screening a deficiency library collection. The majority of these mutations sorted into six complementation groups, five of which have been identified as alleles of brahma (brm), moira (mor) osa, pointed (pnt), and polycephalon (poc). osa, brm, and mor encode proteins with homology to SWI1, SWI2, and SWI3, respectively, suggesting that the activity of a SWI/SNF chromatin-remodeling complex has an important impact on E2F-dependent phenotypes. Mutations in poc also suppress phenotypes caused by p21(CIP1) expression, indicating an important role for polycephalon in cell-cycle control.

Animals↗
PubMed1999

The SERRATE locus controls the formation of the early juvenile leaves and phase length in Arabidopsis.

The development of the shoot can be divided into a series of distinct developmental phases based on leaf character-istics and inflorescence architecture. The relationship between phase length, defined by the number of organs produced, and the timing of the floral induction (V3-I1 transition) is relatively ill defined. Characterization of the serrate mutant (CS3257; Arabidopsis Biological Research Center) revealed defects in both vegetative and inflores-cence phase lengths, the timing of phase transitions, leaf number, the leaf initiation rate, and phyllotaxy. The timing of floral induction, however, is the same as in wild-type in extended short days as well as in short days, whereas the flowering time response to photoperiod is unaffected. SERRATE is shown to be required for the development of early juvenile leaves (V1) and to promote late juvenile leaf development (V2), while suppressing adult leaf (V3) and inflorescence development (I1 and I2). The se mutation supports the hypothesis that the timing of floral induction is independent of vegetative and inflorescence phase lengths. The role of SERRATE in the regulation of phase length and leaf identity is discussed.

Arabidopsis↗
PubMed1992

Fetal compensation of the hemolytic anemia in mice homozygous for the normoblastosis (nb) mutation.

The mouse autosomal recessive mutation nb causes a deficiency of erythroid ankyrin and generates a life-threatening hemolytic anemia in adult mice; however, at birth, nb/nb mice appear to be robust and show no pallor. In our study, the time of disease onset was sought by comparison of nb/nb and +/? mice both in utero and postnatally. Erythroid ankyrin messenger RNA (mRNA) is expressed in fetal erythroid progenitors from normal mice, but is reduced to 10% of normal levels in mutant fetuses. Despite the deficiency of erythroid ankyrin mRNA, 16 and 18 day nb/nb fetuses have normal levels of red blood cells (RBCs) and the RBCs are morphologically normal by scanning electron microscopy. The earliest signs of any clinical anomaly are an increase in the number of circulating reticulocytes and the deposition of minor amounts of iron just before birth in the 18 day fetal nb/nb liver, suggesting that RBCs are being destroyed. Within 24 hours after birth, nb/nb neonates have a slight but significant decrease of their RBC counts. During the next 5 days, the nb/nb RBC counts decrease markedly, the reticulocyte counts assume the mutant adult levels of 60%, the erythrocytes become microcytic and fragmented, and iron deposits accumulate in the liver. The rapid onset of clinical disease postnatally, coupled with our findings that the erythroid ankyrin gene is transcribed in fetal erythroid cell precursors from normal mice, suggest that mechanisms exist in the nb/nb fetus to compensate for the erythroid ankyrin deficiency.

Aging↗
PubMed1997

ACL5: an Arabidopsis gene required for internodal elongation after flowering.

In rosette plants, the formation of initial flowers is closely linked to the lengthening of internodes (bolting). In order to clarify the molecular basis of bolting, mutants with reduced lengths of internodes were screened. This paper presents the identification and characterization of recessive mutations in ACAULIS5 (ACL5), a gene required for internodal growth in Arabidopsis thaliana. Unlike previously described mutants with reduced size of organs, the acl5 mutant has a severe defect that is restricted to the process of cell elongation after transition to the reproductive stage and shows no phenotype before floral induction. The results of RNA blot hybridizations showed that the acl5 mutation causes a striking reduction in the transcript levels of genes encoding the tonoplast intrinsic protein (gamma-TIP) and the endoxyloglucan transferase (EXGT-A1), both of which have recently been suggested to be important for cell elongation. Furthermore, our morphological study indicates that the mutation also causes proliferative arrest of the apical inflorescence meristem. These results strongly suggest that, during the reproductive phase, the wild-type ACL5 gene product has a critical function not only in the control of elongation growth of organs but also in the continued maintenance of the proliferative activity of flower-producing meristems.

Arabidopsis↗
PubMed1999

Molecular characterization of phenylalanine hydroxylase deficiency in Chile. Mutations in brief no. 243. Online.

Both the haplotype distribution and the mutational spectrum of the phenylalanine hydroxylase (PAH) gene has been defined for the Chilean phenylketonuria (PKU) population. Mutation analysis was performed using a combined approach of screening for common European and Oriental mutations and application of the DGGE scanning method in the remaining uncharacterized alleles. A total of 16 different mutations have been identified, including two novel ones, Q232X and IVS11nt5. The most frequent mutations were IVS10nt-11 and V388M present both in the 13% of the mutant chromosomes. The rest of the mutations are rare. The haplotype association including VNTR and STR alleles, was examined to investigated the origin and distribution of PAH alleles in Chile. Our results are consistent with Southern Europeans as the major source of PAH mutations in Latin America. However, we have also detected mutations from East and Central Europe, such IVS12nt1, R408W and R252W. It is clear that the PKU mutation present in each Latin American country varies with the demographic profile and specific mutation scanning is necessary in each population both for diagnostic and prognostic purposes. The correlation between the genotypes and the phenotypes is consistent with the emerging pattern of mutation severity deduced from previous studies in related populations.

Chile↗
PubMed1995

CSF-1 treatment promotes angiogenesis in the metaphysis of osteopetrotic (toothless, tl) rats.

It has recently been shown that following treatment with colony-stimulating factor-1 (CSF-1) the osteopetrotic condition in toothless (tl) rats greatly improves and growth is accelerated. We have examined the effects of such treatment on the microvasculature of the distal femoral chondro-osseous junction, a site where bone growth in length is coordinated with angiogenesis. Vascular casts and ultrastructural analyses of this region showed that, compared to untreated normal rats, untreated mutants showed little bone growth or angiogenesis. When mutants were treated with CSF-1 angiogenesis was markedly accelerated. These data show a remarkable effect of this growth factor on angiogenesis in this osteopetrotic mutation. Whether this effect of CSF-1 on angiogenesis is direct or indirect is not known and indicates that its effects on the normal microvasculature deserve further study.

Animals↗
PubMed1997

Photo and hormonal control of meristem identity in the Arabidopsis flower mutants apetala2 and apetala1.

We have analyzed the contributions of phytochrome and gibberellin signal transduction to the control of flower meristem identity in the Arabidopsis mutants apetala1 (ap1) and apetala2 (ap2). ap1 flowers are partially defective for the establishment of flower meristem identity and are characterized by the production of ectopic secondary or axillary flowers and by branching. Axillary flower production is also induced in ap2-1 flowers by short-day photoperiod and is suppressed by hy1, a mutation blocking phytochrome activity. The production of axillary flower by ap2-1 is also suppressed by exogenous gibberellins and by spindly (spy), a mutation that activates basal gibberellin signal transduction in hormone-independent manner. Ectopic axillary flower production and floral branching by ap1 flowers are also suppressed by spy. We conclude that gibberellins promote flower meristem identity and that the inflorescence-like traits of ap2-1 and ap1-1 flowers are due in part to SPY gene activity.

Arabidopsis↗
PubMed2006

Porphyromonas gingivalis galE is involved in lipopolysaccharide O-antigen synthesis and biofilm formation.

Porphyromonas gingivalis is a crucial component of complex plaque biofilms that form in the oral cavity, resulting in the progression of periodontal disease. To elucidate the mechanism of periodontal biofilm formation, we analyzed the involvement of several genes related to the synthesis of polysaccharides in P. gingivalis. Gene knockout P. gingivalis mutants were constructed by insertion of an ermF-ermAM cassette; among these mutants, the galE mutant showed some characteristic phenotypes involved in the loss of GalE activity. As expected, the galE mutant accumulated intracellular carbohydrates in the presence of 0.1% galactose and did not grow in the presence of galactose at a concentration greater than 1%, in contrast to the parental strain. Lipopolysaccharide (LPS) analysis indicated that the length of the O-antigen chain of the galE mutant was shorter than that of the wild type. It was also demonstrated that biofilms generated by the galE mutant had an intensity 4.5-fold greater than those of the wild type. Further, the galE mutant was found to be significantly susceptible to some antibiotics in comparison with the wild type. In addition, complementation of the galE mutation led to a partial recovery of the parental phenotypes. We concluded that the galE gene plays a pivotal role in the modification of LPS O antigen and biofilm formation in P. gingivalis and considered that our findings of a relationship between the function of the P. gingivalis galE gene and virulence phenotypes such as biofilm formation may provide clues for understanding the mechanism of pathogenicity in periodontal disease.

Biofilms↗
PubMed2001

The mouse slalom mutant demonstrates a role for Jagged1 in neuroepithelial patterning in the organ of Corti.

The Notch signalling pathway has recently been implicated in the development and patterning of the sensory epithelium in the cochlea, the organ of Corti. As part of an ongoing large-scale mutagenesis programme to identify new deaf or vestibular mouse mutants, we have identified a novel mouse mutant, slalom, which shows abnormalities in the patterning of hair cells in the organ of Corti and missing ampullae, structures that house the sensory epithelia of the semicircular canals. We show that the slalom mutant carries a mutation in the Jagged1 gene, implicating a new ligand in the signalling processes that pattern the inner ear neuro-epithelium.

Animals↗
PubMed1985

The morphology, physiology, and neural projections of supernumerary compound eyes in Drosophila melanogaster.

Supernumerary compound eyes in Drosophila melanogaster produced by the extra eye (ee) mutation were analyzed with regard to their morphology, physiology, and neural projections. Electron and light microscopy revealed that large extra eyes often possess the normal complement of compound-eye cell types and that these cells usually have standard fine structure. In addition, the array of photoreceptor cell rhabdomeres within individual supernumerary ommatidia is standardly trapezoidal, and ommatidial subpopulations having mirror-image configurations of their rhabdomeric trapezoids are separated by an equator in extra eyes. Light stimulation of supernumerary eyes can elicit photoreceptor depolarization potentials as evidenced by electroretinographic recordings from them. In addition, extra-eye photoreceptor cells have a functional pupillary response to light stimulation. Although the supernumerary eyes can be functionally and anatomically standard, examination of serial, silver-stained sections of extra-eye heads has shown that their photoreceptor axons seldom innervate the brain. This situation obtains even in a case in which the normal, ipsilateral compound eye was removed by the eyeless mutation. In contrast, rare supernumerary antennae occasionally found in ee stocks have receptor cells whose axons innervate ventral brain. In addition to duplications of cuticular epithelia, extra glial cells, muscle fibers, and ocellar interneurons are sometimes found in extra-eye bearing flies. Discussion of these results focuses on a polarity guidance hypothesis which models the growth of adult photoreceptor axons into the brain during normal development.

Animals↗
PubMed1999

Evidence of decreased adhesion between the neural retina and retinal pigmented epithelium of the Mitfvit (vitiligo) mutant mouse.

In order for the retina to function properly, photoreceptor cell outer segments must be in contact with the adjacent retinal pigmented epithelium (RPE). A mouse model homozygous for the vitiligo mutation of the microphthalmia (Mitf) gene manifests disruption of the outer segment/RPE interdigitation and demonstrates progressive loss of the photoreceptor cells. The mouse nevertheless has near normal levels of rhodopsin for many weeks and it is not known whether there is an in vivo loss of adhesion or whether the disruption is visible following tissue processing for histology. To assess this, a mechanical separation experiment was performed in which neural retinas were peeled free from the RPE and examined for the amount of pigment adherent to them. The peeling experiment indicated that control neural retinas retained significant amounts of adherent pigment at all ages examined. Neural retinas of mutant mice at age 2 weeks demonstrated adherent pigment, but older animals retained minimal pigment. Scanning electron microscopy indicated that the RPE cells of control mice were markedly damaged upon peeling and displayed different planes of cleavage, whereas those of mutants showed minimal cellular damage upon peeling, suggestive of decreased adhesion. A recombination experiment revealed that the mutant RPE/eyecup could reappose mutant and control retinas under in vitro conditions, suggesting that RPE fluid transport abilities were intact. The data provide the first direct experimental evidence that the Mitfvit mutant mouse has a naturally occurring retinal detachment and hence support its value as a model for studies of retina/RPE adhesion.

Animals↗
PubMed2005

Auxin response factors ARF6 and ARF8 promote jasmonic acid production and flower maturation.

Pollination in flowering plants requires that anthers release pollen when the gynoecium is competent to support fertilization. We show that in Arabidopsis thaliana, two paralogous auxin response transcription factors, ARF6 and ARF8, regulate both stamen and gynoecium maturation. arf6 arf8 double-null mutant flowers arrested as infertile closed buds with short petals, short stamen filaments, undehisced anthers that did not release pollen and immature gynoecia. Numerous developmentally regulated genes failed to be induced. ARF6 and ARF8 thus coordinate the transition from immature to mature fertile flowers. Jasmonic acid (JA) measurements and JA feeding experiments showed that decreased jasmonate production caused the block in pollen release, but not the gynoecium arrest. The double mutant had altered auxin responsive gene expression. However, whole flower auxin levels did not change during flower maturation, suggesting that auxin might regulate flower maturation only under specific environmental conditions, or in localized organs or tissues of flowers. arf6 and arf8 single mutants and sesquimutants (homozygous for one mutation and heterozygous for the other) had delayed stamen development and decreased fecundity, indicating that ARF6 and ARF8 gene dosage affects timing of flower maturation quantitatively.

Arabidopsis↗
PubMed1988

Molecular analysis of an unstable P element insertion at the singed locus of Drosophila melanogaster: evidence for intracistronic transposition of a P element.

In a companion study, a number of P element insertions into the singed locus were characterized. Here is reported a detailed analysis of the structure and mutability of another P element insertion at sn, known as sncm. Under conditions which mobilize P elements, sncm mutates at high frequency to both wild-type (sn+) and to a much more extreme allele (snext). Wild-type revertants appear to represent precise or nearly precise excisions of the P element. Certainly two, and most likely all five, of the snext alleles studied result from the insertion of a duplicate copy of this P element into a nearby site in an inverted orientation. We propose a model in which both the sn+ and snext mutational events can be explained by excision of the P element from one chromatid followed by reintegration into the sister chromatid at a nearby site (intracistronic transposition). Finally, it is shown that the snext alleles are themselves unstable and the structure of a resulting chromosome aberration is examined.

Alleles↗
PubMed1996

Type-I collagen mutation compromises the post-yield behavior of Mov13 long bone.

Despite recent advances in our understanding of the molecular basis of skeletal fragility, little is known about how these molecular alterations lead to whole bone brittleness. In the current study, we investigated the relationship between a type-I collagen mutation and post-yield behavior of whole bone in Mov13 transgenic mice by considering tissue-level organizational issues known to be important for normal bone fracture. Mechanical assays revealed that the post-yield deflection of Mov13 femurs was reduced by 61% relative to littermate controls. Fractographic images revealed that lamellar interfaces which were important for dissipating energy during the failure process of control femurs, were not effective in Mov13 mice. Further investigation revealed that a 22% reduction in bone collagen content, a 2-fold increase in tissue porosity, and significant alterations in collagen organization interfered with normal energy dissipation mechanisms of Mov13 microstructure. Collectively, the results provided the first evidence that the reduced ductility associated with a type-I collagen mutation was mediated by alterations in intermediate structures that normally contribute to the post-yield behavior of cortical bone. The results suggest that, to better understand the pathogenesis of skeletal fragility, it is important to consider the effects of molecular alterations on higher-level structures, particularly those structures that contribute to the failure mechanisms in normal bone.

Animals↗
PubMed2002

Clinical features of a form of Hirschsprung's disease caused by a novel genetic abnormality.

BACKGROUND/PURPOSE: The aim of this report is to describe the pattern of similarities among the patients, exemplifying a newly recognized form of Hirschsprung's disease (HSCR) caused by mutations of ZFHX1B encoding Smad interacting protein-1. METHODS: Fluorescence in situ hybridization (FISH) using several cDNAs and RP11-BAC clones and mutation gene scanning using direct nucleotide sequencing analysis of polymerase chain reaction (PCR) were conducted. Personal records of the patients also were analyzed retrospectively to confirm the clinical features. RESULTS: All the patients represented isolated cases without any familial tendency. Aganglionic segments were limited to the recto-sigmoid colon in 3 cases and the rectum in one. Chromosomal screening found normal karyotypes in all cases except one, in whom a translocation between chromosomes 2 and 13 was detected. In addition to HSCR, characteristic facial appearance (hypertelorism with strabismus and wide nasal bridge), microcephaly with epilepsy, and severe physical and mental disabilities were found in all the patients. FISH for the patient having the chromosomal abnormality showed that about a 5-Mb cytogenetic deletion flanked at the 2q22 translocation breakpoint. Among 3 genes mapping to this deleted region, 2 nonsense mutations and a 4-base pair deletion were detected in ZFHX1B. CONCLUSIONS: The clinical features of the patients have surprising resemblance and constitute a wide spectrum of neurocristopathies. These findings suggest that the ZFHX1B may be a very important gene for normal embryonic neural crest development. These also indicate that the HSCR can be regarded as a congenital malformation with a background of a multigenetic neurocristopathy. It is of great interest that mutations were located at the same spot (exon 8) of ZFHX1B in 3 of 4 cases, probably accounting for the unique clinical features of this newly recognized form of HSCR.

Adult↗
PubMed1989

Genes directing flower development in Arabidopsis.

We describe the effects of four recessive homeotic mutations that specifically disrupt the development of flowers in Arabidopsis thaliana. Each of the recessive mutations affects the outcome of organ development, but not the location of organ primordia. Homeotic transformations observed are as follows. In agamous-1, stamens to petals; in apetala2-1, sepals to leaves and petals to staminoid petals; in apetala3-1, petals to sepals and stamens to carpels; in pistillata-1, petals to sepals. In addition, two of these mutations (ap2-1 and pi-1) result in loss of organs, and ag-1 causes the cells that would ordinarily form the gynoecium to differentiate as a flower. Two of the mutations are temperature-sensitive. Temperature shift experiments indicate that the wild-type AP2 gene product acts at the time of primordium initiation; the AP3 product is active later. It seems that the wild-type alleles of these four genes allow cells to determine their place in the developing flower and thus to differentiate appropriately. We propose that these genes may be involved in setting up or responding to concentric, overlapping fields within the flower primordium.

Alleles↗
PubMed2002

Stereocilia defects in waltzer (Cdh23), shaker1 (Myo7a) and double waltzer/shaker1 mutant mice.

Mutations in myosin VIIa (Myo7a) and cadherin 23 (Cdh23) cause deafness in shaker1 (sh1) and waltzer (v) mouse mutants respectively. In humans, mutations in these genes cause Usher's syndrome type 1B and D respectively, as well as certain forms of non-syndromic deafness. Examination of the organ of Corti from shaker1 and waltzer mice has shown that these genes are required for the proper organisation of hair cell stereocilia. Here we show that at embryonic day 18.5, the outer hair cells of Cdh23(v) homozygote mutant mice appear immature, projecting fewer recognisable stereocilia than heterozygote controls, and by post-natal day (P) 4 their stereocilia are arranged in a disorganised pattern rather than in the regular 'V'-shape seen in heterozygotes. Inner hair cell stereocilia are also disorganised in Cdh23(v) mutant homozygotes. Myo7a was expressed normally in the hair cells of P0 Cdh23(v2J) mutants demonstrating that cadherin 23 is not required for Myo7a expression at this stage. No stereocilia defects were observed in P4 Cdh23(v)/Myo7a(4626SB) double heterozygotes (+/Cdh23(v) +/Myo7a(4626SB)) and neither the Cdh23(v) nor Myo7a(4626SB) homozygote phenotypes were affected by the presence of one mutant copy of Myo7a or Cdh23 respectively. The hair cell phenotype of double homozygote mutant mice did not differ from single Myo7a(4626SB) homozygote mutants. Finally, we found no significant correlation between loss of hearing and double heterozygosity for mutations in Cdh23 and Myo7a in mice aged between 7.5 and 10 months. These findings suggest that Cdh23 and Myo7a are both required for establishing and/or maintaining the proper organisation of the stereocilia bundle and that they do not genetically interact to affect this process nor to cause age-related hearing loss.

Alleles↗