PubMed Health⌕ Search

Biomedical subjects

H Winking

Publications and source records attributed to H Winking.

At least 55 records · Page 3Linked to original sources
PubMed1991

Adoptive transfer of the hematopoietic system of trisomic mice with limited life span: stem cells from six different trisomies are capable of survival.

The life span of murine trisomies is limited to the fetal or early postnatal period. However, rescue of the hematopoietic system of fetal mice with trisomies (Ts) 12, 13, 14, 16, 18, and 19 is possible by transplanting hematopoietic stem cells from the liver into lethally irradiated adult hosts. Thus, radiation chimeras with permanent and almost complete trisomic hematopoietic and lymphocytopoietic systems were constructed. The longest documented survival of a trisomic graft was 12 months in Ts 19 chimeras. Blood counts in trisomic chimeras reveal a marked anemia in Ts 16 chimeras; lymphocytopenia in Ts 12, Ts 16, and Ts 19 chimeras; and granulocytopenia in Ts 18 chimeras. Survival rates of Ts 12, Ts 18, and Ts 19 chimeras were not different from those of the respective controls, whereas survival rates of chimeras with Ts 13 and Ts 16 hematopoiesis were markedly reduced and that of Ts 14 chimeras only slightly reduced. These results indicate that transplanted hematopoietic stem cells from Ts 13, Ts 14, and Ts 16 fetuses exhibit relevant genetically determined defects, resulting in a reduced restoration capacity of hematopoietic organs and/or deficiencies of differentiated blood cells.

Animals↗
PubMed1991

Polymorphic HSRs in chromosome 1 of the two semispecies Mus musculus musculus and M. m. domesticus have a common origin in an ancestral population.

HSRs (homogeneously staining regions) are the cytological correlates of DNA amplification. In the house mouse, Mus musculus, many populations are polymorphic for the presence or absence of HSRs on chromosome 1. In the semispecies M. m. domesticus the amplified DNA is present within one HSR, whereas in M. m. musculus chromosomes 1 with two HSRs are found. Hybridization of HSR-specific probes to Southern blots of HSR-carrying genomic DNAs from different localities and semispecies revealed similar complex band patterns. The remaining variation is restricted to sequences with a low degree of amplification. Variation is higher between semispecies than within one semispecies. It is assumed that HSRs are derived from one original amplification event and that unequal recombination is the mechanism underlying the length variation of HSRs present today in both semispecies. Evidence from G-banding and in situ hybridization shows that the two HSRs of M. m. musculus originated from a single HSR by means of a paracentric inversion, where one break-point was located within the single HSR and the second outside the HSR. As a consequence of the paracentric inversion the two HSRs of M. m. musculus are permanently linked together. Since exchange of genes between the two semispecies is restricted to a narrow hybrid zone the amplification that gave rise to the HSR most probably occurred prior to the divergence into the semispecies M. m. domesticus and M. m. musculus about 1 million years ago.

Animals↗
PubMed1991

Histochemically demonstrable catecholamines in the sympathetic nervous system of trisomic 16 and normal fetal mice.

The formaldehyde-induced fluorescence (FIF) and micro-spectrofluorometric techniques were used to study catecholamines in the sympathetic nervous system of normal and trisomy 16 fetal mice with a gestation age of 15 days, an animal model for human trisomy 21 (Down's syndrome). FIF intensity in the stellate sympathetic ganglion of trisomic embryos did not differ from that of controls, whereas in the adrenal medulla the FIF intensity was 38% less in trisomic than in control embryos. When adrenal medullary cells from embryos with a gestational age of 15 days were maintained in culture for 7-10 days, a difference in FIF intensity between groups was still evident. The rate of noradrenaline uptake in cultured adrenal medullary cells also was significantly less in trisomic than in control fetal mice. The results suggest that the development of adrenal medulla is slowed in trisomic 16 mice and that uptake of noradrenaline by trisomic adrenal medullary cells is impaired.

Adrenal Medulla↗
PubMed1991

Pathogenesis of various forms of double outlet right ventricle in mouse fetal trisomy 13.

The pathogenesis of double outlet right ventricle with or without pulmonary infundibular atresia in mouse fetal trisomy 13 was studied at the organ level using microdissection and scanning electron microscopy. Altogether, 394 karyotyped trisomic embryos were collected between 11 days and 16 hours of gestation (presence of a vaginal plug = day 1) and 15 days of gestation at intervals of 8 hours, and at 16 days of gestation. The hearts were perfusion-fixed, microdissected, and prepared to be observed in scanning electron microscope in the following standardized orientations: frontal, right or left profile, septal and parietal halves of the right ventricle and outflow tract (conotruncus). Comparison of 276 trisomic hearts with their normal counterparts described previously has shown that: the first pathognomonic feature is the abnormal anterior position of the proximal part of the parietal outflow tract ridge or of both ridges (at 12 days and 16 hours of gestation); the abnormal anterior fusion of these ridges ("coalescence") results in a mesenchymal mass behind which is deviated the pulmonary part of the outflow tract lumen; from 14 days and 16 hours of gestation on, this lumen is either obstructed, resulting in a supravalvar stenosis of the pulmonary trunk and subsequently evolving into double outlet right ventricle with pulmonary infundibular atresia; or, in a minority of cases, this lumen is not obstructed and the heart develops into double outlet right ventricle without pulmonary infundibular atresia. The pathogenesis of these malformations differs from most of the known hypotheses based on deductions from human malformed hearts, as well as from observations of the pathogenesis of similar outflow tract malformations, such as those found in the Keeshond dog or rats treated with trimethadione.

Animals↗
PubMed1991

Microclones derived from the mouse chromosome 7 D-E bands map within the proximal region of the c14CoS deletion in albino mutant mice.

A group of radiation-induced perinatal-lethal deletions that include the albino (c) locus on mouse chromosome 7 causes failure of expression of various hepatocyte-specific genes when homozygous (S. Gluecksohn-Waelsch, 1979, Cell 16:225-237). The transcription of such genes could be controlled in trans by a regulatory gene(s) located within the proximal region of the C14CoS deletion. To identify this potential regulatory gene, a microclone library was established from microdissected D and E bands of chromosome 7. Three nonoverlapping microclones (E305, E336B, and E453B) hybridizing with wildtype but not with C14CoS/C14CoS DNA were isolated. E336B represents a single-copy DNA fragment, whereas E305 and E453B hybridized with 3 and 10 EcoRI DNA restriction fragments, respectively. All fragments map exclusively within the deletion. The microclones hybridized to DNA of viable C6H/C14CoS deletion heterozygotes but not to DNA of homozygotes for the lethal mutation c10R75M, which belongs to the same complementation group as c14CoS. DNA of viable homozygous mutant C62DSD, which carries a deletion breakpoint proximal to that of c6H, hybridized only with E453B. This microclone identified 6 EcoRI restriction fragments in C62DSD/C62DSD DNA. The results demonstrate that of the isolated microclones, E453B identifies a locus (D7RT453B) that maps closest to the hsdr-1 (hepatocyte-specific developmental regulation) locus (S. Gluecksohn-Waelsch, 1989, Mouse Newslett. 83: 149), which maps between the proximal breakpoints of deletions c10R75M and c62DSD.

Albinism↗
PubMed1991

Incidence of double-band HSRs in chromosome 1 of the house mouse, Mus musculus musculus, from Oland (Sweden): a population study.

The incidence of homogeneously staining regions (HSRs) in chromosome no. 1 of Mus musculus musculus was ascertained by C-band staining on chromosomes of mice collected on the island of Oland (Sweden). A total of 157 specimens from eight localities representing three regions were analysed. Mice with enlarged chromosome no. 1, due to double-band HSRs, were found in all three regions. The overall incidence of HSR-bearing chromosomes was 6.7% in mice collected on Oland in 1988. In the two largest samples, the incidences were 14.5% (n = 31) and 3.9% (n = 76). With regard to HSR size, several different variants were present. Size differences were found for the proximal as well as for the distal HSR band. Different mutant forms were found even within one population (a single farm). The implications of these findings are discussed.

Animals↗
PubMed1991

Transcripts from amplified sequences of an inherited homogeneously staining region in chromosome 1 of the house mouse (Mus musculus).

Several populations of the house mouse, Mus musculus, are polymorphic for the presence or absence of an inherited homogeneously staining region (HSR) in chromosome 1. The HSR consists of highly amplified DNA sequences, present in low copy numbers in the HSR- genome. A cloned HSR-derived genomic sequence detected transcripts of about 1.3 and 4.5 kb on blots of poly(A)+ RNA from liver of HSR+ mice but not from that of HSR- mice. A cDNA library was established from RNA of HSR+ mice and screened with the HSR-derived genomic clone. Positive clones were isolated and shown to be complementary to the 1.3-kb RNA species and to amplified DNA sequences in the HSR+ genome. The combined sequence of four overlapping cloned cDNAs is 959 nucleotides long and includes an open reading frame encoding a putative protein of 208 amino acids. The pertinent gene is unidentified. No homologous sequence is stored in the EMBL data base. A stretch of 109 nucleotides at the 3' end of the 1.3-kb RNA homology region in the same genomic fragment, as indicated by hybridization data and sequence motifs resembling promoter elements. Thus, our data suggest that at least two genes or gene families are encoded in the HSR.

Amino Acid Sequence↗
PubMed1990

Protamine amount and cross linking in mouse teratospermatozoa and aneuploid spermatozoa.

The level of SH-group oxidation in spermatozoa from the cauda epididymis was measured by a cytofluorometric method in chromosomally normal mice and two chromosome mutants. The first one, a tertiary trisomic karyotype (Ts(1(13]7OH), is characterized by severe oligospermia and high levels (approximately 75%) of malformed spermatozoa. The second, a hybrid between two European feral mouse stocks, is heterozygous for multiple Robertsonian translocations and produces exclusively aneuploid spermatozoa. Neither the severe teratospermiogenesis nor the severe aneuploidy was reflected in total SH-group fluorescence values nor in free SH-group fluorescence. It is concluded that both the production of protamines and protamine cross linking by S-S bridge formation are rather autonomous processes during spermatogenesis because 1) the increased DNA variance of the aneuploid spermatozoa is not reflected in an increased variance of the total and free SH-groups, 2) aneuploidy for the protamine gene carrying chromosome 16 is not reflected by the SH-group values for individual spermatozoa, and 3) protamine production and cross linking are independent of the mild to severe terataspermiogenesis in the tertiary trisomic karyotype.

Aneuploidy↗
PubMed1990

Kinetics of oogenesis in mice heterozygous for Robertsonian translocation.

The total number of oocytes at different postmating time intervals (18-40 days) was determined in mice homozygous and heterozygous for different Robertsonian (Rb) translocations, of both laboratory and feral origin. The number of oocytes was lower in heterozygous than in homozygous mice throughout the period studied. Independently of the genetic background (i.e. laboratory or feral), structural heterozygosity had a progressive detrimental effect on oocyte numbers: open, or chain diakinetic configurations had a greater detrimental effect than close, or ring, configurations. The genetic background, however, affected the ovarian constitution in terms of the total number of germ cells, which are more numerous in laboratory than in feral mice. The kinetics of oogenesis seems to be faster in feral than in laboratory mice. At the light of the data here presented, and of those already available from the literature on male and female gametogenesis in conditions of structural heterozygosity, it appears that factors other than unsaturation of pairing sites or interference with pachytene X-chromosome inactivation have to be considered. In the wild, the reduced oocyte numbers in Rb heterozygous female can contribute to the retention of isolated populations in contact zones.

Animals↗
PubMed1990

Fragile sites induced by 5-azacytidine and 5-azadeoxycytidine in the murine genome.

The cytosine analogues 5-azacytidine and 5-azadeoxycytidine were used to induce fragile sites on mouse chromosomes. Sites of relative frequent fragility were ascertained and compared with fragile sites induced by the antimetabolites methotrexate, fluorodeoxyuridine and aphidicolin as reported previously. Considerable overlap of fragile sites induced by the very different agents is evident. Fragile sites are common to all chromosomes and most of them are susceptible to different modes of induction.

Animals↗
PubMed1990

Nondisjunction, disturbances in spindle structure, and characteristics of chromosome alignment in maturing oocytes of mice heterozygous for Robertsonian translocations.

To correlate the chromosomal constitution of meiotic cells with possible disturbances in spindle function and the etiology of nondisjunction, we examined the spindle apparatus and chromosome behavior in maturing oocytes and analyzed the chromosomal constitution of metaphase II-arrested oocytes of CD/Cremona mice, which are heterozygous for a large number of Robertsonian translocation chromosomes (18 heterobrachial metacentrics in addition to two acrocentric chromosomes 19 and two X chromosomes). Spreading of oocytes during prometaphase 1 revealed that nearly all oocytes of the heterozygotes contained one large ring multivalent, apart from the bivalents of the two acrocentric chromosomes 19 and the X chromosomes, indicating that proper pairing and crossing-over between the homologous chromosome arms of all heterobrachial chromosomes took place during prophase. A large proportion of in vitro-matured oocytes arrested in metaphase II exhibited numerical chromosome aberrations (26.5% hyperploids, 40.8% hypoploids, and 6.1% diploids). In addition, some of the oocytes with euploid chromosome numbers (26.5% of the total examined) appeared to be nullisomic for one chromosome and disomic for another chromosome, so that aneuploidy levels may even be higher than expected on the basis of chromosome counts alone. Although oocytes of the complex heterozygous mice seemed able initially to form a bipolar spindle during first prometaphase, metaphase I spindles were frequently asymmetrical. Chromosomes in the multivalent did not align properly at the equator, centromeres of neighboring chromosomes in the multivalent remained maloriented, and pronounced lagging of chromosomes was observed at telophase I in oocytes obtained from the Robertsonian translocation heterozygotes. Therefore, disturbance in spindle structure and chromosome behavior appear to correlate with the chromosomal constitution in these oocytes and, ultimately, with failures in proper chromosome separation. In particular, reorientation appears to be a rare event, and malorientation of chromosomes may remain uncorrected throughout prometaphase, as we could not find many typical metaphase I stages in heterozygotes. This, in turn, could be the basis for malsegregation at anaphase and may ultimately induce a high rate of nondisjunction and aneuploidy in the oocytes of CD/Cremona mice, leading to total sterility in heterozygous females.

Aneuploidy↗
PubMed1990

Nuclear transfer from teratocarcinoma cells into mouse oocytes and eggs.

A spontaneous ovarian teratocarcinoma was isolated from a LT/Sv mouse female and converted into an ascites tumor from which embryonal carcinoma (EC) cells were dissociated. Non-enucleated and enucleated, activated oocytes were fused with EC cells and either cultured in vitro or transferred into ligated oviducts of Swiss/A females. The nucleocytoplasmic hybrids cultured in vitro up to 22 h were examined cytologically at various time intervals. EC nuclei showed morphological remodelling in the foreign cytoplasm. EC chromosomes and female pronuclear chromosomes together formed a common metaphase. The nucleocytoplasmic hybrids developed in vivo were analyzed cytologically between the first and third day after oviduct transfer. The majority of embryos developed abnormally and, in a few instances, they had passed several cleavage divisions and reached, at best, a developmental stage resembling a premature morula. Fertilized, enucleated eggs were fused with EC cells or microinjected with EC nuclei. The resulting nucleocytoplasmic hybrids were either cultured in vitro or in vivo up to the fourth day. Enzyme tests were carried out on the nuclear transplant embryos, using electrophoretic variants of glucose phosphate isomerase (GPI) in order to distinguish between EC nuclei (GPI-A) and recipient eggs (GPI-B). The EC-specific GPI could be detected in about one third of the embryos analyzed and, in several instances, also together with the egg-specific GPI. Most of them were arrested during early cleavage divisions. Some embryos cleaved abnormally or mimicked normal embryogenesis. In a few instances, development resulted in embryos that resembled late preimplantation embryos.

Animals↗
PubMed1990

Serological H-Y antigen and gonadal status in XYDOM sex-reversed mice.

Y chromosomes of feral mice (Mus musculus domesticus) from various localities, when introduced into the C57BL/6 laboratory strain, give rise to phenotypic females and true hermaphrodites both with the sex chromosome constellation XY. Sex-reversed animals of each type were examined macroscopically or histologically for gonadal status and H-Y antigenic activity by serological assay methods. Most XY females with histologically confirmed bilateral ovaries did not differ from XX female controls with respect to serological H-Y antigen, i.e. they were H-Y negative. The true hermaphrodites were H-Y positive, though H-Y antigenic activity was intermediate to male and female controls in the majority of cases. The findings support a relationship between the presence of serological H-Y antigen and gonadal status.

Animals↗
PubMed1989

The influence of the Robertsonian translocation Rb(X.2)2Ad on anaphase I non-disjunction in male laboratory mice.

A Robertsonian translocation in the mouse between the X chromosome and chromosome 2 is described. The male and female carriers of the Rb(X.2)2Ad were fertile. A homozygous/hemizygous line was maintained. The influence of the X-autosomal Robertsonian translocation on anaphase I non-disjunction in male mice was studied by chromosome counts in cells at metaphase II of meiosis and by assessment of aneuploid progeny. The results conclusively show that the inclusion of Rb2Ad in the male genome induces non-disjunction at the first meoitic division. In second metaphase cells the frequency of sex-chromosomal aneuploidy was 10.8%, and secondary spermatocytes containing two or no sex chromosome were equally frequent. The Rb2Ad males sired 3.9% sex-chromosome aneuploid progeny. The difference in aneuploidy frequencies in the germ cells and among the progeny suggests that the viability of XO and XXY individuals is reduced. The pairing configurations of chromosomes 2, Rb2Ad and Y were studied during meiotic prophase by light and electron microscopy. Trivalent pairing was seen in all well spread nuclei. Complete pairing of the acrocentric autosome 2 with the corresponding segment of the Rb2Ad chromosome was only seen in 3.2% of the cells analysed in the electron microscope. The pairing between the X and Y chromosome in the Rb2Ad males corresponded to that in males with normal karyotype. Reasons for sex-chromosomal non-disjunction despite the normal pairing pattern between the sex chromosomes may be seen in the terminal chiasma location coupled with the asynchronous separation of the sex chromosomes and the autosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphase↗
PubMed1989

Immunocytogenetics. III. Analysis of trivalent and multivalent configurations in mouse pachytene spermatocytes by human autoantibodies to synaptonemal complexes and kinetochores.

Mice heterozygous for one or more Robertsonian (Rb) translocation chromosomes have been used to analyze synaptonemal complex (SC) configurations and kinetochore arrangements in trivalents and multivalents. Rb heterozygosity without arm homologies leads to the formation of heteromorphic trivalents in meiosis I; alternating homology of the chromosome arms produces ringlike or chainlike multivalents. Immunofluorescence double-labeling with human antibodies to SCs and kinetochores was performed on surface-spread pachytene spermatocytes. Both Rb bivalents and Rb trivalents clearly showed that metacentrics possess only one centromere. In heteromorphic trivalent SCs, the nonhomologous kinetochores of the two acrocentrics were closely paired in a cis-configuration and juxtaposed opposite the kinetochore of the metacentric; the latter appeared to be an integral part of the longitudinal SC axis. Meiotic multivalents of interpopulation hybrids included up to 36 chromosome arms. In multivalent SCs, the kinetochores always lay together, with the SC arms arranged away from the central centromere cluster. The paracentromeric regions of the Rb chromosomes appeared to remain unsynapsed on both sides of the centromeres. The SC arms were often linked by end-to-end associations. Following desynapsis of the multivalent SC, the kinetochores of the Rb metacentrics showed a highly nonrandom topologic distribution within the nucleus, reminiscent of their arrangement during synapsis.

Animals↗
PubMed1988

Behavioural and developmental abnormalities in mouse trisomy 19: an animal model of mental retardation induced by chromosome imbalance.

Murine trisomy 19 (Ts19) can be regarded as a general model of human trisomies. It is the only autosomal trisomy in the mouse that survives the perinatal period. Therefore, it is the only animal model available for postnatal investigations of trisomy-specific mental retardation. To evaluate the extent of developmental retardation during the late-embryonic and fetal period of gestation, total body weight development was documented for 60 Ts19-fetuses and compared with that of 219 euploid in utero-mates. In addition, a postnatal study on body-weight development of 77 Ts19-neonates and 74 euploid littermates was performed starting on day 1 postpartum and continuing until spontaneous death or until day 22. Forty-seven Ts19-individuals were further tested in nine behavioural test systems in order to determine their neurophysiological developmental profile. Findings were compared with age-dependent morphologic and physiologic parameters. The data obtained in the present study show a significant retardation of organ- and body-weight development in Ts19-mice starting on day 14 of gestation. Retardation of physiological parameters is progressive and persists throughout the perinatal and postnatal periods. Furthermore, the trisomic individuals showed specific behavioural abnormalities.

Age Factors↗
PubMed1988

Restriction fragment polymorphism in the sex-determining region of the Y chromosomal DNA of European wild mice.

Using 32P-labeled probe consisting mainly of (GATA)n we have shown that a male specific Alu1 DNA blot pattern which defines the Y chromosome sex-determining locus in inbred mice is highly polymorphic in wild mice, indicating substantial sequence evolution in this region under field conditions. In all cases examined by in situ hybridization, the region concerned is paracentromeric. In contrast, the blot pattern of another probe (M 34) which detects repeated sequences specific to the mouse Y chromosome but outside the sex-determining locus, remains constant between different isolates.

Animals↗