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Biomedical subjects

L M Silver

Publications and source records attributed to L M Silver.

At least 55 records · Page 3Linked to original sources
PubMed1996

Low frequency of mouse t haplotypes in wild populations is not explained by modifiers of meiotic drive.

t haplotypes are naturally occurring forms of mouse chromosome 17 that show non-mendelian transmission from heterozygous +/t males. In laboratory studies, transmission ratios of > or = 0.90 or higher are typically observed. With transmission ratios of this level, theoretical analyses predict high frequencies of t haplotypes (approximately 75%) in wild populations. In contrast, empirical frequencies of only 15-25% are typically found. This has led to the suggestion that modifiers of drive may play a role in reducing t frequencies. We have measured transmission ratio distortion (TRD) levels in wild +/t mice to examine this hypothesis. TRD was very high in both litters collected from wild-caught pregnant females, and in wild litters bred in the laboratory (mean = 0.9). Contrary to the results of other studies, we found no difference in TRD levels between semilethal and lethal t haplotypes nor between litters conceived from cycling or postpartum estrus. We found three litters with aberrantly low TRDs that were all multiply sired, although the role this might play in natural populations is unknown. These findings show a general absence of modifiers of drive in natural populations and suggest that other factors are responsible for the low observed frequencies of wild t haplotypes.

Animals↗
PubMed1996

The Cairo spiny mouse Acomys cahirinus shows a strong affinity to the Mongolian gerbil Meriones unguiculatus.

The classification of the African spiny mice (genus Acomys) within the Muridae family of rodents has been fraught with controversy. Morphological data suggest a close affinity between this group and true old world mice of the genus Mus. However, the combined results of immunological, biochemical, and DNA melting studies suggest that spiny mice should not even be considered as members of the Murinae subfamily. To further elucidate the position of the spiny mice within the rodent phylogenetic tree, we performed a direct sequence comparison of a 583-nucleotide homologous region from the spiny mouse type species Acomys cahirinus and five other representative rodent species. Our results provide incontrovertible evidence to support the contention that the spiny mouse is more closely related to the Mongolian gerbil Meriones unguiculatus than it is to Mus musculus.

Animals↗
PubMed1995

Conservation of the T-box gene family from Mus musculus to Caenorhabditis elegans.

Recently, a novel family of genes with a region of homology to the mouse T locus, which is known to play a crucial, and conserved, role in vertebrate development, has been discovered. The region of homology has been named the T-box. The T-box domain of the prototypical T locus product is associated with sequence-specific DNA binding activity. In this report, we have characterized four members of the T-box gene family from the nematode Caenorhabditis elegans. All lie in close proximity to each other in the middle of chromosome III. Homology analysis among all completely sequenced T-box products indicates a larger size for the conserved T-box domain (166 to 203 residues) than previously reported. Phylogenetic analysis suggests that one C. elegans T-box gene may be a direct ortholog of the mouse Tbx2 and Drosophila omb genes. The accumulated data demonstrate the ancient nature of the T-box gene family and suggest the existence of at least three separate T-box-containing genes in a common early metazoan ancestor to nematodes and vertebrates.

Amino Acid Sequence↗
PubMed1995

Identification, characterization, and localization to chromosome 17q21-22 of the human TBX2 homolog, member of a conserved developmental gene family.

The T-box motif is present in a family of genes whose structural features and expression patterns support their involvement in developmental gene regulation. Previously, sequence comparisons among the T-box domains of ten vertebrate and invertebrate T-box (Tbx) genes established a phylogenetic tree with three major branches. The Tbx2-related branch includes mouse Mm-Tbx2 and Mm-Tbx3, Drosophila optomotor-blind (Dm-Omb), and Caenorhabditis elegans Ce-Tbx2 and Ce-Tbx2 and Ce-Tbx7 genes. From the localization of Mm-Tbx2 to Chromosome (Chr) 11, we focused our search for the human homolog, Hs-TBX2, within a region of synteny conservation on Chr 17q. We used Dm-Omb polymerase chain reaction (PCR) primers to amplify a 137-basepair(bp)_ product from human genomic, Chr 17 monochromosome hybrid, and fetal kidney cDNA templates. The human PCR product showed 89% DNA sequence identity and 100% peptide sequence identity to the corresponding T-box segment of Mm-Tbx2. The putative Hs-TBX2 locus was isolated within a YAC contig that included three anonymous markers, D17S792, and D17S948, located at Chr 17q21-22. Hybridization-and PCR-based screening of a 15-week fetal kidney cDNA library yielded several TBX2 clones. Sequence analysis of clone lambda omicron TBX2-1 confirmed homology to Mm-TBx2-90% DNA sequence identity over 283 nt, and 96% peptide sequence identity over 94 amino acids. Similar analysis of Hs-TBX2 cosmid 154F11 confirmed the cDNA coding sequence and also identified a 1.7-kb intron located at the same relative position as in Mm-Tbx2. Phylogenetic analyses of the T-box domain sequences found in several vertebrate and invertebrate species further suggested that the putative human TBX2 and mouse Tbx2 are true homologs. Northern blot analysis identified two major TBX2 expression fetal kidney and lung; and in adult kidney, lung, ovary, prostate, spleen, and testis. Reduced expression levels were seen in heart, white blood cells, small intestine, and thymus. These results suggest that Hs-TBX2 could play important roles in both developmental and postnatal gene regulation.

Amino Acid Sequence↗
PubMed1995

Complementary deoxyribonucleic acid cloning and characterization of mSP-10: the mouse homologue of human acrosomal protein SP-10.

Complementary DNA encoding the putative mouse homologue for human acrosomal protein SP-10, a candidate contraceptive vaccinogen, was cloned and sequenced. The entire open reading frame (amino acids 18 to 261) of the mouse SP-10 (mSP-10), with the exception of the signal peptide (amino acids 1 to 17), was placed under the influence of inducible T7 RNA polymerase/promoter system to overproduce recombinant protein (re-mSP-10) in Escherichia coli. A six-histidine tag, which was coexpressed at the carboxyl terminus of re-mSP-10, provided the means for purification of re-mSP-10 by immobilized metal chelation affinity chromatography technique. The level of purity of re-mSP-10 thus obtained was determined by 2-dimensional gel electrophoresis to be 98%. Immunoblotting with monoclonal and polyclonal antibodies previously generated against human or baboon SP-10 showed that mSP-10 shared significant antigenic similarity with its primate counterparts. The position of mSP-10 in the mouse genome was next mapped through segregation analysis of an interspecific backcross panel of 96 animals. Acrv1 (assigned gene symbol for mSP-10) was localized in the proximal portion of mouse chromosome 9 in a region that exhibits synteny with human 11q23, the region to which ACRV1 (gene symbol for human SP-10) was previously mapped. These characterizations by combined immunological and gene mapping techniques established the cloned mSP-10 to be the mouse homologue of SP-10.

Acrosome↗
PubMed1994

An ancient family of embryonically expressed mouse genes sharing a conserved protein motif with the T locus.

The T locus encodes a product with DNA binding activity that is likely to play a role in the development of all vertebrate organisms. We have identified and characterized a novel family of mouse genes that share a protein motif, the T-box, with the prototypical T locus. The T-box domain of the T locus co-localizes with its DNA binding activity. Each T-box gene is expressed in a unique temporal and spatial pattern during embryogenesis. Phylogenetic analysis suggests that at least three T-box genes were present in the common ancestor to vertebrates and invertebrates. Thus, members of the T-box family could have played a role in the evolution of all metazoan organisms.

Amino Acid Sequence↗
PubMed1993

Hybrid sterility-6: a mouse t complex locus controlling sperm flagellar assembly and movement.

Mouse t haplotypes alter sperm differentiation, resulting in abnormal sperm movement and sterility. In previous studies, a locus responsible for hybrid sterility in the genus Mus,Hst-4, was mapped to the distal inversion of the t complex on chromosome 17. Here we report the identification and characterization of two additional hybrid sterility loci, Hst-5 and Hst-6, that map to the same inversion. We further show that an abnormality in sperm flagellar curvature deriving from interactions between t haplotypes and the M. spretus allele of Hst-6 is indistinguishable from one exhibited by sperm from mice carrying two t haplotypes. Additionally, we demonstrate that this latter phenotype maps to the distal inversion of t haplotypes. Morphological and functional studies of Hst-6 mutant sperm also imply that the product(s) of Hst-6 is a spermatogenic-specific protein, important for assembly and function of the sperm axoneme. Thus, Hst-6 provides direct access to the molecular basis of t haplotype-specific alterations in sperm function that emanate from the t complex distal inversion.

Alleles↗
PubMed1993

High-resolution comparative mapping of mouse chromosome 17.

We have constructed a high-resolution genetic linkage map spanning the proximal 32 cM of mouse chromosome 17 including the t complex. Simple sequence repeats at D17Tu1 and D17Mit6 were employed to identify 121 recombinants among 374 offspring of a (C57BL/6 x CAST/Ei) x C57BL/6 backcross. In contrast to previously reported interspecific Mus domesticus x Mus spretus backcrosses, we did not observe inversion polymorphisms with our cross. This and the relatively high frequency of DNA polymorphisms between C57BL/6 and CAST/Ei allowed us to put 32 RFLV markers and 32 PCR markers on a single map. We present the localization of four new DNA markers and determined map positions for 10 other loci, which previously had been assigned to intervals of the t complex only through the study of partial t haplotype chromosomes.

Animals↗
PubMed1993

The peculiar journey of a selfish chromosome: mouse t haplotypes and meiotic drive.

Mouse t haplotypes are descendents of a variant form of chromosome 17 that evolved the ability to propagate itself at the expense of the wild-type homolog from heterozygous +/t males. Although once enigmatic, these widespread selfish chromosomes have revealed many of their secrets in response to a combined assault with molecular, genetic and phylogenetic techniques. This review summarizes the current understanding of t haplotypes and their raison d'être.

Animals↗
PubMed1993

The mouse t complex distorter-3 (Tcd-3) locus and transmission ratio distortion.

A novel central partial t haplotype was generated by screening for a recombination event between overlapping distal and proximal partial haplotypes. This haplotype contains just two elements--Tcrt and Tcd-3t--involved in the t-specific transmission ratio distortion phenotype. Breeding analysis of males that carry this chromosome provides evidence that Tcd-3 is, indeed, a distorter locus and not a second responder. Furthermore, the data indicate that a single well-defined distorter locus is insufficient to overcome completely the self-destructive, low transmission ratio distortion phenotype expressed by the t allele at the t complex responder locus, although a small, but highly significant, effect was observed.

Alleles↗