Biomedical subjects

H Winking

Publications and source records attributed to H Winking.

At least 37 records · Page 2Linked to original sources

PubMed1996

Distortion of Mendelian recovery ratio for a mouse HSR is caused by maternal and zygotic effects.

An HSR in chromosome 1 which is found in many feral populations of Mus musculus domesticus was shown in previous studies to consist of a high-copy long-range repeat cluster. One such cluster, MUT, showed distorted transmission ratios when introduced by female parents. MUT/+ offspring were preferentially recovered at the expense of +/+ embryos in the progeny of male MUT/+ x female +/+ but were found at the expected 1:1 ratio in reciprocal crosses. Preferential recovery of maternal MUT was due to lethality of postimplantation +/+ embryos. There was no distortion of the recovery ratio in MUT/+ x MUT/MUT progeny: maternal MUT and + clusters were present among live implants at a 1:1 ratio. Maternal and zygotic effects therefore contribute to the phenomenon. The mechanism of their interaction is unknown.

Animals↗

PubMed1996

Copy numbers of a clustered long-range repeat determine C-band staining.

A cluster of long-range repeats (LRRs) with a repeat size of roughly 100 kb is part of band D of chromosome 1 of the house mouse, Mus musculus. The cluster is cytogenetically polymorphic: it is either C-band negative or C-band positive. Our results show that the differential staining behavior depends on the LRR copy number and not on differences in DNA composition. There is a threshold between 105 and 175 LRR copies per haploid genome; clusters with lower copy numbers stain C-band negative, whereas those with higher copy numbers are C-band positive. Above this threshold, the size of the C-band is linearly correlated with the LRR copy number. The results imply that sequences capable of forming heterochromatin may be dispersed throughout the genome but are not recognized as such by cytogenetic techniques, unless they reach the threshold amount and concentration.

Animals↗

PubMed1995

Loss of telomeric sites in the chromosomes of Mus musculus domesticus (Rodentia: Muridae) during Robertsonian rearrangements.

Mouse chromosomes possessing multiple Robertsonian rearrangements (Rb chromosomes) have been examined using fluorescence in situ hybridization with the telomeric consensus sequence (TTAGGG)n. No hybridization signals were detected at the primary constriction of Rb chromosomes. This observation leads us to conclude that the formation of Rb chromosomes in the mouse is invariably associated with the loss of telomeric regions. More significantly, a further alteration in regions flanking the primary constrictions was observed after hybridizing with a minor satellite DNA probe to Rb chromosomes. It seems likely that the breakpoints required for a Robertsonian process do not include telomeric sites exclusively but extend to the adjacent pericentromeric regions of the original acrocentric chromosomes. In contrast to previous reports, these observations demonstrate the elimination of substantial amounts of chromosomal DNA during the formation of mouse Rb chromosomes.

Animals↗

PubMed1995

A member of the mouse LRR transcript family with homology to the human Sp100 gene.

A previously isolated cDNA sequence with homology to the long-range repeat (LRR) cluster in chromosome 1 of the house mouse, Mus musculus, was identified as derived from a 1.3 kb polyadenylated RNA. This transcript belongs to a family of polyadenylated RNAs which are synthesized from a multicopy gene included in the LRR copies. The representation of the 1.3 kb transcript in genomic DNA was studied in lambda and cosmid clones from the LRR cluster. Two different types of LRRs were detected with respect to the arrangement of coding regions. In the type-1 arrangement, the sequence is split into five exons, and in the type-2 arrangement, into six exons. The respective exons with their flanking regions were sequenced. The analysis of splice signals revealed that LRR copies with a type-1 arrangement are presumably the source of the 1.3 kb transcript. The 1.3 kb transcript has sequence homology to a human gene encoding Sp100, a nuclear antigen recognized by autoantibodies from patients suffering from some autoimmune diseases including primary biliary cirrhosis. Mouse exons II and III exhibit 71% homology at the nucleotide level and 56% homology at the amino acid level to the human Sp100 cDNA. We mapped the human Sp100 gene to chromosome 2. This location corroborates the assumption that the human Sp100 gene and the mouse LRR gene are homologous, as the human chromosome 2 contains the segment which is homologous to the mouse LRR region.

Amino Acid Sequence↗

PubMed1995

A transcript family from a long-range repeat cluster of the house mouse.

A family of closely related genes is a component of the polymorphic long-range repeat cluster D1Lub1 of the house mouse. Members of the gene family have diverged from one another by rearrangements and point mutations. D1Lub1 cluster have low (approximately 50) or high (> or = 500) copy numbers. In mice with high-copy clusters five or six poly(A)+ RNAs are found, while in mice with low-copy clusters only a single member of the RNA family is detected. The RNA family is synthesized in a tissue-independent manner. Each member of the RNA family is defined by a set of DNA probes. Cross hybridization with the probes reveals common 5' regions and variable remaining parts. The RNA variants are probably transcribed from different gene copies.

Animals↗

PubMed1995

Establishment of permanent wild-mouse cell lines with readily identifiable marker chromosomes.

Physical gene mapping by in situ hybridization is a difficult task in an all-acrocentric mouse karyotype, because all of the chromosomes are morphologically very similar. These difficulties can be overcome by using the many different metacentric Robertsonian translocation (Rb) chromosomes derived from wild mice. Here we describe the establishment of two Moloney murine leukemia virus-transformed suspension cell lines, WMP-1 and WMP-2, derived from wild mice of the strain WMP/WMP. These mice carry nine pairs of metacentric Rb chromosomes containing chromosomes 1 to 18. Chromosome 19 and the sex chromosomes are the only acrocentric chromosomes. Furthermore, a heterozygous reciprocal translocation between chromosomes 13 and 17 involved in two Rb chromosomes is present in this stock and provides additional marker chromosomes. The chromosome designation of these mice is Rb(10.17)9Mpl Rb(13.15)10Mpl T(13.17)1Lub.

Animals↗

PubMed1994

Synaptonemal complexes of chains and rings in mice heterozygous for multiple Robertsonian translocations.

Complex Robertsonian translocation heterozygosities in the mouse have been used to test different hypotheses regarding the correlation between male hybrid sterility and chromosomal abnormality. Synaptonemal complexes of meiotic super-chains and super-rings involving 15 to 18 metacentric chromosomes were studied in relation to spermatogenic histology. Both types of multivalents showed a characteristic pachytene pattern of alternating paired and non-paired segments. The amount of unpaired segments in rings was about 18% and in chains about 23% of the total length of multivalent chromosomes. The meiotic chains were associated with the proximal part of the X chromosomes in more than 60% of pachytene cells; a similar tight proximity of rings with X or Y chromosomes was never found. Complete arrest of germ cell maturation correlated with super-chains and inconspicuous testicular histology with super-rings. This demonstrates that an excessive amount of unpaired chromosomal axes does not lead per se to male infertility through gametogenic breakdown. On the contrary, the results clearly indicate spermatogenic impairment in this system of multimetacentric heterozygosity as a reflection of X chromosome super-chain interference.

Animals↗

PubMed1993

Organization of the Y chromosome in testis cells of fetal, subadult and adult mice as determined by in situ hybridization.

In order to reveal the time-course of decondensation of the Y chromosome in Sertoli cells, testes preparations of fetal, subadult and adult laboratory mice in different developmental stages were hybridized in situ with biotinylated probe pY353/B, which binds along the entire long arm of the mouse Y chromosome. All fetal and subadult testicular cells exhibited tightly compacted hybridization signals, indicating highly condensed Y chromosomes. Diffuse signals, indicating decondensation of the Y chromosome were found for the first time in the structurally differentiated Sertoli cells of 35 to 40 day old animals. Since this coincides with the appearance of mature sperm nuclei, a correlation between decondensation of the Y chromosome and its activity in sperm maturation and/or sperm motility can be presumed.

Animals↗

PubMed1993

Evolution of a long-range repeat family in chromosome 1 of the genus Mus.

Copy numbers and variation of a clustered long-range repeat family on chromosome (Chr) 1 have been studied in different species of the genus Mus. The repeat sequence was present in all, as inferred from cross-hybridization with probes derived from the Mus musculus repeat family. Copy numbers determined by dot blot hybridization were very low, from three to six per haploid genome in M. caroli, M. cervicolor, and M. cookii. These species form one branch of the phylogenetic tree in the genus Mus. In the other group of phylogenetically related species--M. spicilegus, M. spretus, M. musculus and M. macedonicus--copy numbers ranged from 6 to 1810 per haploid genome. The repeat cluster is cytogenetically visible as a fine C-band in M. macedonicus and as a C-band positive homogeneously staining region (HSR) in several populations of M. m. domesticus and M. m. musculus. When cytogenetically visible, the clusters contained from 179 to 1810 repeats. Intragenomic restriction fragment length polymorphisms (RFLPs), which reflect sequence variation among different copies of the long-range repeat family, increased with higher copy numbers. The high similarity of the RFLP pattern among genomes with C-band positive regions in Chr 1 of M. m. musculus, M. m. domesticus, and M. macedonicus points to a close evolutionary relationship of their Chr 1 repeat families.

Animals↗

PubMed1993

Meiotic synapsis of homogeneously staining regions (HSRs) in chromosome 1 of Mus musculus.

About 50 copies of a long-range repeat DNA family with a repeat size of roughly 100 kb and with sequence homology to mRNAs are clustered in the G-light band D of chromosome 1 of the house mouse, Mus musculus. We studied amplified versions of the cluster which are found in many wild populations of M. musculus. They are cytogenetically conspicuous as one or two C-band positive homogeneously staining regions (single- and double band HSRs) which increase the mitotic length of chromosome 1. The double band HSR was phylogenetically derived from a single band HSR by a paracentric inversion. In homozygous condition, such HSRs contribute, albeit not as much as expected from their mitotic length, to the synaptonemal complex (SC) length of chromosome 1. In HSR heterozygous animals an elongation of the SCs was not noticeable. In single band HSR heterozygous males, synapsis proceeds regularly and continuously from the distal telomere towards the centromeric end without forming buckles. Thus, the single band HSR has no adverse effect on pairing. The same straight pairing behaviour was found in the majority of double band HSR heterozygous spermatocytes. This shows that extensive nonhomologous pairing can take place in the earliest phase of synapsis. Synapsis was discontinuous, leaving the central part of the bivalent 1 asynapsed, in only 14.3% of double band HSR heterozygous cells. In such cells the chromosome 1 SC is completed at a later stage of meiosis. The delay is presumably an effect of the inversion that includes one HSR band and the segment between the two HSR bands.

Animals↗

PubMed1993

Mouse fetal trisomy 13 and hypotrophy of the spinal cord: effect on calbindin-D28k and calretinin expressed by neurons of the spinal cord and dorsal root ganglia.

Trisomy 13 was detected in 10% of mouse embryos obtained from pregnant females which were doubly heterozygous for Robertsonian chromosomes involving chromosome 13. The developing dorsal root ganglia and spinal cords were examined in trisomy 13 and littermate control mice between days 12 and 18 of gestation (E12-18). The overall size of the dorsal root ganglia and number of ganglion cells within a given ganglion were not altered, but the number of neurons immunoreactive for calbindin and calretinin was reduced. The trisomic spinal cord was reduced in size with neurons lying in a tightly compact distribution in the gray matter. In trisomic fetuses, the extent of the neuropil of the spinal cord was reduced, and may represent a diminished field of interneuronal connectivity, due to reduced arborization of dendritic processes of the neurons present, particularly of calbindin-immunostained neurons. Furthermore, the subpopulation of calretinin-immunoreactive neurons and axons was also reduced in developing trisomic gray and white matter, respectively. Thus, overexpression of genes on mouse chromosome 13 exerts a deleterious effect on the development of neuropil, affecting both dendritic and axonal arborization in the trisomy 13 mouse. The defect of calbindin or calretinin expression by subsets of dorsal root ganglion or spinal cord neurons may result from deficient cell-to-cell interactions with targets which are hypoplastic.

Animals↗

PubMed1993

Zoogeography of the chromosome 1 HSR in natural populations of the house mouse (Mus musculus).

A polymorphism of the central part of chromosome 1 has been described from natural populations of the house mouse (Mus musculus). The region shows up as a C band-positive homogeneously staining region (HSR) under the light microscope. M. m. domesticus mice carry single band HSRs, whereas M. m. musculus animals have double band HSRs. HSR size variations have been described in both subspecies. The frequency of the HSR chromosome 1 in populations varies from 4% to 81%, but none of the large samples examined consisted only of homozygotes. In the subspecies M. m. domesticus, HSRs were found in North Africa and Western Europe, mainly in the hilly regions of Southern Germany and Switzerland. Localities with double HSRs are distributed all over the area of M. m. musculus. Based on the population data presented and DNA similarity of different HSRs, the origin and distribution of HSR chromosomes in the house mouse are discussed.

Animals↗

PubMed1993

Further examination of the kinetics of gonadal development in XY female mice.

Y-chromosomes derived from house mouse populations of Mus domesticus are able to lead to the formation of XY females (i.e. hermaphrodite individuals with both ovarian and testicular tissues) when inserted, by appropriate crosses, into the C57BL/6J genome, which usually carries the Mus musculus Y chromosome. An abnormal interaction between the testis-determining gene on the Y (of domesticus origin) and an autosomal recessive allele (of musculus origin) needed for testicular formation is the likely explanation of this phenomenon. In the present paper we analyse the histological kinetics of gonadal development in hermaphrodites obtained by introducing the Y chromosomes from wild living house mice [from Zagreb, (Croatia) and Hohenentringen (Southern Germany)] into the C57BL/6J genome. Among 88 individuals, 9 XY hermaphrodites were detected, 6 before birth and 3 afterwards. The percentage of the ovarian-type tissues in the ovotestes fell drastically between day 18 of fetal life and day 20 after birth. These findings corroborate and extend those already published for other Y domesticus chromosomes and stress the possible role of Y chromosome differentiation in speciation processes.

Aging↗

PubMed1992

Functions of estrogens and anti-estrogens in the rat endometrial adenocarcinoma cell lines RUCA-I and RUCA-II.

Inbred rats of the DA/Han and BDII/Han strains have been proposed as suitable model systems for studying hormonal carcinogenesis, because they die mainly from hormone-dependent endometrial adenocarcinoma. Here we characterize the RUCA-I cell line derived from an endometrial adenocarcinoma of an inbred DA/Han rat and the RUCA-II cell line derived from an endometrial adenocarcinoma of an inbred BDII/Han rat. The RUCA-I cell line, if transplanted to the neck of female DA/Han rats, gives rise to endometrial adenocarcinomas at the ectopic site. The morphology of these ectopically grown tumors is predominantly of the moderately differentiated sub-class. In contrast, ectopic tumor growth of the RUCA-II cell line can be observed only if cells are transplanted to athymic nude mice. Biochemically, both cell lines are characterized by the stable expression of estrogen receptors. However, no statistically significant mitotic response of RUCA-I and RUCA-II cells to estradiol was measurable, and no induction of expression of the progesterone receptor by estradiol was detectable, although estradiol transformed the estrogen receptor into its stable DNA-binding state. In contrast, the rate of proliferation of RUCA-I but not of RUCA-II cells was reduced in the presence of 10(-6) M tamoxifen. From these results we conclude that (i) both cell lines, RUCA-I and RUCA-II, represent a new and promising endometrial tumor model; (ii) the mechanism of the hormone-dependent growth regulation of RUCA-I and RUCA-II cells is obviously impaired; (iii) the RUCA-I cell line appears to be a suitable model system for the study of molecular aspects of estrogen- and tamoxifen-dependent gene expression.

Adenocarcinoma↗

PubMed1992

Evolution of a B2 tagged sequence from a long-range repeat family in the genus Mus.

A long-range repeat family of more than 50 kb repeat size is clustered in Chromosomes (Chr) 1 of Mus musculus and M. spretus. In M. musculus this long-range repeat family shows considerable variation of copy-number frequency and contains coding regions for at least two genes. In an intron of a gene, which is part of the repeat, a B2 small interspersed repetitive element (SINE) is inserted at identical positions. The B2 element is present in all copies of the long-range repeat family; it was presumably a component of the ancestral single-copy precursor sequence that gave rise by amplification to the repeat family. Copies of the long-range repeat family vary with respect to the number of TAAA tandem repeats in the A-rich 3' end region of the B2 element. As inferred from polymerase chain reaction (PCR) data, presence and frequency of repeat number variants in the (TAAA)n block are strain and species specific. The B2 element and its flanking regions were sequenced from two copies of the long-range repeat family. Sequence divergence between the two copies (only non-CG base substitutions and deletions/insertions) was determined to be 2.6%. Based on the drift rate in human Alu elements and a correction for the higher drift rates in rodents, an estimate for the divergence time of 1.7 million years was calculated. Since the long-range repeat family is present in M. musculus and M. spretus, it must have evolved by amplification before the separation of the two species about 1-4 million years ago.

Animals↗

PubMed1992

A long-range repeat cluster in chromosome 1 of the house mouse, Mus musculus, and its relation to a germline homogeneously staining region.

The laboratory mouse C57BL genome contains about 50 copies of a long-range repeat DNA family clustered in the C-D region of chromosome 1. The repeat length is more than 50 kb and includes sequences homologous to at least two mRNAs. There are small differences in the copies of this repeat family such as restriction site mutations and gross differences like rearrangements and insertions of LINE1 elements. A germline homogeneously staining region occurring as a chromosome 1 polymorphism in many feral populations of the house mouse is an amplified version of this long-range repeat cluster.

Animals↗

PubMed1992

Genetic mapping and assignment of a long-range repeat cluster to band D of chromosome 1 in Mus musculus and M. spretus.

A cluster (D1Lub1) of a long-range repeat family was mapped to the proximal part of the Giemsa-negative band D in Chromosome 1 of Mus musculus and M. spretus by in situ hybridization with cloned probes of the long-range repeat family. By making use of restriction fragment length polymorphisms in DNAs from interspecific backcross mice, the cluster could be mapped to a position 5.3 +/- 2.1 cM distal to the Inha locus and the same distance proximal to the Bcl-2 locus. D1Lub1 was inseparable in 114 meiotic events from Acrg, Sag, and Akp-3. Taken together, the data may serve as a reference for coordinating the genetic and cytogenetic maps of Mus Chromosome 1. High-copy-number variants of the cluster, which appear cytogenetically as homogeneously staining regions at the same chromosome location, presumably arose by amplification of the long-range repeat family in situ.

Animals↗

PubMed1992

Aberrant Myc expression in the murine trisomy 15 syndrome is correlated with prolonged proliferation in spongiotrophoblast cells of the placenta.

In the mouse the protooncogene Myc is localized to Chromosome 15. Embryos with trisomy 15 (Ts15) are severely retarded and die in utero at an early stage. The placenta of these embryos shows enlargement of the fetal spongiotrophoblast. In the spongiotrophoblast and giant cells of the normal euploid placenta, Myc expression declines from day 10.5 of gestation onward whereas Myc expression persists at a high level in Ts15 cells. At the same time these Ts15 cells show prolonged proliferation which consequently leads to the observed enlargement of that tissue layer in Ts15 placentas.

Animals↗