The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.

/pdf/genome-sequence-of-the-brown-norway-rat-yields-insights-into-51an5rofp3.pdf

Genome sequence of the Brown Norway rat yields insights into mammalian evolution

The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality ‘draft’ covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.

Genome sequence of the Brown Norway rat yields insights into mammalian evolutionRat Genome Sequencing Project ConsortiumNature200442849352115057822

One: Reptiles.- Strike-Induced Chemosensory Searching by Rattlesnakes: The Role of Envenomation-Related Chemical Cues in the Post-Strike Environment.- Fossil and Comparative Evidence for Possible Chemical Signaling in the Mammal-Like Reptiles.- Two: Vomeronasal Organ.- Snake Tongue Flicking Behavior: Clues to Vomeronasal System Functions.- The Accessory Olfactory System: Role in Maintenance of Chemoinvestigatory Behavior.- Flehmen Behavior and Vomeronasal Organ Function.- Three: Neuroendocrinology of Olfaction.- Olfaction in Central Neural and Neuroendocrine Systems: Integrative Review of Olfactory Representations and Interrelations.- The Neuroendocrinology of Scent Marking.- Four: Chemical Signals and Endocrines.- Priming Pheromones in Mice.- Pheromonal Control of the Bovine Ovarian Cycle.- Synchronizing Ovarian and Birth Cycles by Female Pheromones.- Volatile and Nonvolatile Chemosignals of Female Rodents: Differences in Hormonal Regulation.- Five: Chemical Signals and Genetics.- Communication Disparities Between Genetically-Diverging Populations of Deermice.- Six: Field Studies (Pheromone Ecology).- The Ecological Importance of the Anal Gland Secretion of Yellow Voles (Lagurus luteus).- Odor as a Component of Trap Entry Behavior in Small Rodents.- Experimental Modulation of Behavior of Free-Ranging Mammals by Semiochemicals.- Seven: Social Odors: Discrimination and Recognition.- Mechanisms of Individual Discrimination in Hamsters.- Human Olfactory Communications.- Eight: Chemistry.- Studies of the Chemical Composition of Secretions from Skin Glands of the Rabbit Oryctolagus cuniculus.- Nine: Pheromones and Other Physiological Functions.- Thermal and Osmolarity Properties of Pheromonal Communication in the Gerbil, Meriones unguiculatus.- Ten: Abstracts.- The Evolution of Alarm Pheromones.- Investigation into the Origin(s) of the Freshwater Attractant(s) of the American Eel.- A Pregnancy Block Resulting from Multiple-Male Copulation or Exposure at the Time of Mating in Deer Mice (Peromyscus maniculatus).- Olfactory Communication in Kangaroo Rats (D. merriami).- Odor Preferences of Young Rats: Production of an Attractive Odor by Males.- Rate and Location of Scent Marking by Pikas During the Breeding Season.- Effects of Urine on the Response to Carrot-Bait in the European Wild Rabbit.- An Investigation into the 'Bruce Effect' in Domesticated Rabbits.- Individual Discrimination on the Basis of Urine in Dogs and Wolves.- Throat-Rubbing in Red Howler Nbnkeys (Alouatta seniculus).- Author Index.

Chemical Signals in Vertebrates 3

The instinctive and species-specific behavioural response of animals to pheromones has intrigued biologists for a long time. Recent molecular and electrophysiological approaches have provided new insights into the mechanisms of pheromone detection in rodents and into the sensory coding of pheromone signals that lead to gender discrimination and aggressive behaviour.

Molecular detection of pheromone signals in mammals: from genes to behaviour.

The ability to recognize individuals is essential to many aspects of social behaviour, such as the maintenance of stable social groups, parent-offspring or mate recognition, inbreeding avoidance and the modulation of competitive relationships. Odours are a primary mediator of individuality signals among many mammals. One source of odour complexity in rodents, and possibly in humans, resides in the highly polymorphic major histocompatibility complex (MHC). The olfactory acuity of mice and rats allows them to distinguish between the urinary odours of congenic strains differing only in single genes within the MHC, although the chemical mediators or odorants are unknown. However, rodent urine also contains a class of proteins, termed major urinary proteins (MUPs), that bind and release small volatile pheromones. We have shown that the combinatorial diversity of expression of MUPs among wild mice might be as great as for MHC, and at protein concentrations a million times higher. Here we show in wild house mice (Mus domesticus) that urinary MUPs play an important role in the individual recognition mechanism.

Individual recognition in mice mediated by major urinary proteins

Transgenic livestock may prove useful for the large scale production of valuable proteins. By targeting expression to the mammary gland these proteins could be harvested from milk. To this end, we have designed a hybrid gene to direct the synthesis of human anti-hemophilic factor IX to the mammary gland, and introduced it into sheep. Two transgenic ewes, each carrying about 10 copies of the foreign gene, have been analysed for expression. Both animals express human factor IX RNA in the mammary gland and secrete the corresponding protein into their milk.

Expression of human anti-hemophilic factor-ix in the milk of transgenic sheep

Gene transfer into animals has considerable potential for livestock improvement. If this potential is to be realized, the ease of generation of transgenic livestock will be of major importance. We report here the production of six transgenic sheep by microinjection of DNA into early embryos (1.2% of embryos transferred). Three different gene constructs were injected and transgenic sheep were obtained with each. The transgenic animals have all incorporated the DNA without detectable rearrangement, and where multiple copies were integrated, they are present in arrays of tandem repeats. Transmission of transferred genes to progeny of three of the sheep has been demonstrated. Five founder transgenic sheep described carry genes designed to direct the production of human clotting factor IX or human αl–antitrypsin in milk. Transgenic animals carrying such genes may ultimately provide a new source of these and other therapeutic proteins.

Gene Transfer into Sheep

Fourteen different major urinary protein (MUP) genomic clones from BALB/c mice were isolated By restriction site mapping, six of these form two sets of three overlapping clones By the criterion of cross-hybridization, the 10 different genes fall into two groups of four (Group 1) and three (Group 2) genes, while three genes fall into neither group Southern blot analysis of genomic DNA with Group 1 and Group 2 plasmid subclones shows that the haploid mouse (BALB/c) genome contains approximately 15 Group 1 genes, 12 Group 2 genes and at least seven MUP genes that belong to neither group An analysis of mouse-Chinese hamster hybrid cell lines shows that most, if not all, Group 1 and Group 2 genes are located on mouse chromosome 4

https://www.embopress.org/doi/pdf/10.1002/j.1460-2075.1982.tb01217.x

Two main groups of mouse major urinary protein genes, both largely located on chromosome 4.

The multigene family which codes for the mouse major urinary proteins (MUPs) consists of approximately 35 genes. Most of these are members of two different groups, Group 1 and Group 2, which can be distinguished by nucleic acid hybridisation. Here we describe the structure of a Group 1 gene and show that two size classes of MUP mRNA which are found in mouse liver result from different splicing events in the 3'-non-coding region and contain different polyadenylation sites. Short mRNA is approximately 750 nucleotides long, contains six exons, and is the main product of the Group 2 genes. Long mRNA is approximately 880 nucleotides long, contains seven exons and is the main product of the Group 1 genes. Five exons and part of the sixth are common to long and short mRNA and contain the coding region. This codes for an acidic protein of 180 amino acids containing an 18 residue signal peptide. A comparison of the mouse sequence with a homologous rat alpha 2u-globulin sequence shows that the rate of evolutionary divergence of the two proteins has been high. Silent sites have diverged four times more rapidly than replacement sites, showing that there has been selection against change in the protein sequence.

https://www.embopress.org/doi/pdf/10.1002/j.1460-2075.1984.tb01925.x

Structure of mouse major urinary protein genes: different splicing configurations in the 3'-non-coding region.

Laboratory mouse strains carry approximately 35 major urinary protein (MUP) genes per haploid genome, tightly clustered together on chromosome 4. Most belong to two main groups (Groups 1 and 2). The available evidence strongly suggests that the Group 1 genes are active while the Group 2 genes are pseudogenes. Here we present the complete sequence of a Group 1 gene and a Group 2 gene and 700 bp of flanking sequence. The sequence of the Group 1 gene is consistent with its being active. The Group 2 gene contains two stop codons and a frame-shift mutation in the reading frame defined by the Group 1 gene, and would code for a signal peptide 25 rather than 19 amino acids long. The Group 2 gene differs from the Group 1 gene in other ways: a deletion upstream of the TATA box and another in intron 3, a base change in the TATA box itself, a 2 bp duplication at the splice acceptor boundary of intron 6, an altered poly(A) addition signal and a 1-base deletion 5' to the initiation codon. Some of these differences may explain the 10- to 20-fold higher level of Group 1 mRNA in mouse liver, and the fact that Group 1 and Group 2 transcripts are mainly spliced differently. The presence of the stop codon means that the Group 2 gene is a pseudogene in the context of the Group 1 gene. However, there is some evidence that the mature hexapeptide that it would code for may have biological activity. The 12 acceptor splice sites of the two genes all contain the identical sequence ACAG at the exon boundary.(ABSTRACT TRUNCATED AT 250 WORDS)

/pdf/sequence-structures-of-a-mouse-major-urinary-protein-gene-5338d9bzrj.pdf

J O Bishop

Papers

Expression of human anti-hemophilic factor-ix in the milk of transgenic sheep

Gene Transfer into Sheep

Two main groups of mouse major urinary protein genes, both largely located on chromosome 4.

Structure of mouse major urinary protein genes: different splicing configurations in the 3'-non-coding region.

Sequence structures of a mouse major urinary protein gene and pseudogene compared.