Chapter 7 Neuropeptide gene expression in transgenic animals

Murphy, David; Ang, Hwee-Luan; Zeng, Qi; Ho, Mei-Yin; Funkhouser, Judith McNiff; Carter, David

doi:10.1016/s0079-6123(08)61166-8

Cited by 7 publications

(3 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that injection of synthetic vasopressin mRNA into the hypothalamic‐neurohypophysial tract of the vasopressin‐deficient Brattleboro rat can reverse the symptoms of diabetes insipidus for up to 5 days (53, 136). Vasopressin mRNAs with a short or absent poly (A) tail were more effectively expressed (84). It was thus suggested that, as magnocellular HNS neurones could apparently selectively accumulate, retrogradely transport and translate exogenous mRNA, intra‐axonal transcripts might participate in a novel mode of neuronal signalling.…”

Section: Somatic Transgenesismentioning

confidence: 99%

“…Neither is the function of this process understood, although two hypotheses have been proposed. Bloom and colleagues have suggested that the vasopressin RNA may act as signalling molecules, carrying the information encoded in the message up and down axons, and maybe even postsynaptically (84, 85). Gainer and Wray (55) have proposed that the axonal transport of specific RNAs may act as a ‘molecular garbage shoot’, rapidly carrying older (deadenylated) messages away from the neural perikaryon, but leaving the newly synthesized mRNAs, which bear long poly (A) tails.…”

Section: Post‐transcriptional Regulation Of Vasopressin Transgenesmentioning

confidence: 99%

See 1 more Smart Citation

In Vivo Gene Transfer Studies on the Regulation and Function of the Vasopressin and Oxytocin Genes

Murphy

Wells

2003

J Neuroendocrinology

View full text Add to dashboard Cite

Novel genes can be introduced into the germline of rats and mice by microinjecting fertilized one-cell eggs with fragments of cloned DNA. A gene sequence can thus be studied within the physiological integrity of the resulting transgenic animals, without any prior knowledge of its regulation and function. These technologies have been used to elucidate the mechanisms by which the expression of the two genes in the locus that codes for the neuropeptides vasopressin and oxytocin is confined to, and regulated physiologically within, specific groups of neurones in the hypothalamus. A number of groups have described transgenes, derived from racine, murine and bovine sources, in both rat and mouse hosts, that mimic the appropriate expression of the endogenous vasopressin and genes in magnocellular neurones (MCNs) of the supraoptic and paraventricular nuclei. However, despite considerable effort, a full description of the cis-acting sequences mediating the regulation of the vasopressin-oxytocin locus remains elusive. Two general conclusions have nonetheless been reached. First, that the proximal promoters of both genes are unable to confer any cell-specific regulatory controls. Second, that sequences downstream of the promoter, within the structural gene and/or the intergenic region that separates the two genes, are crucial for appropriate expression. Despite these limitations, sufficient knowledge has been garnered to specifically direct the expression of reporter genes to vasopressin and oxytocin MCNs. Further, it has been shown that reporter proteins can be directed to the regulated secretory pathway, from where they are subject to appropriate physiological release. The use of MCN expression vectors will thus enable the study of the physiology of these neurones through the targeted expression of biologically active molecules. However, the germline transgenic approach has a number of limitations involving the interpretation of phenotypes, as well as the large cost, labour and time demands. High-throughput somatic gene transfer techniques, principally involving the stereotaxic injection of hypothalamic neuronal groups with replication-deficient adenoviral vectors, are now being developed that obviate these difficulties, and which enable the robust, long-lasting expression of biologically active proteins in vasopressin and oxytocin MCNs.'Neurobiology still has a long way to go to contend with consciousness. Perhaps we should be content to work instead on unconsciousness for a while, and find out about all those processes going on in our brains that we don't know about directly and need science to tell us the answers' (Sydney Brenner) (1).In vivo gene transfer (transgenic) techniques enable the study of any gene sequence within the physiological and developmental integrity of the whole animal. In this review, we describe the work of a number of laboratories, including our own, on the application of transgenesis to the study of the regulation and function of the neurones of the hypothalamic-neurohypophysial system ...

show abstract

Section: Somatic Transgenesismentioning

confidence: 99%

Section: Post‐transcriptional Regulation Of Vasopressin Transgenesmentioning

confidence: 99%

In Vivo Gene Transfer Studies on the Regulation and Function of the Vasopressin and Oxytocin Genes

Murphy

Wells

2003

J Neuroendocrinology

View full text Add to dashboard Cite

show abstract

“…Bloom and co-workers suggested that the VP mRNA may serve as a possible signalling molecule, carrying necessary information encoded in the message up and down axons and, possibly, even postsynaptically (Murphy et al, 1992;MaciejewskiLenoir et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Neurohormones: oxytocin, vasopressin and related peptides – structure, genes, receptors, and evolution

Kochman¹

2013

J. Anim. Feed Sci.

View full text Add to dashboard Cite

Considered biologically as well as philosophicallyABSTRACT. Oxytocin (OT) and vasopressin (VP), and all related hormones, consist of nine amino acids with cysteine residues in positions 1 and 6 that form a six-amino acid cyclic part, and of a C-terminal glycine in α-amidated form. These neuropeptides are classified into oxytocin and vasopressin families based on the amino acid residue at position 8. OT-like and VP-like peptides are present in every vertebrate species. These peptides are a very ancient family of hormones having representatives in diverse species of invertebrates. Invertebrates have either a vasopressin-family peptide or an oxytocin-family peptide, whereas bony fishes, the ancestors of land vertebrates, have both isotocin and vasotocin. Presently, two evolutionary structural lineages have been proposed: an isotocin-mesotocin-OT line, associated with reproductive functions, and a vasotocin-VP line participating in water homeostasis. The ancestral gene encoding the precursor protein has been present in the animal genome for a period exceeding 500 million years of evolution. The exceptionally high stability of this structure of nine-amino acid peptides during the entire process of evolution suggests very powerful selective pressure, possibly by evolution together with respective receptors and specific processing enzymes. A novel gene with a distinct function and expression appeared during evolution through duplication of an ancestral gene. The synteny and order of genes in the neurohypophysial hormone gene locus are conserved in the lamprey, elephant shark, coelacanth, and tetrapods, but disrupted in teleost fishes presumably due to the rearrangements facilitated by a whole-genome duplication event in the teleost fish ancestor. 284 Evolution of neurohormones

show abstract

Neuron-specific expression and physiological regulation of bovine vasopressin transgenes in mice.

Ang¹,

Carter²,

Murphy³

1993

The EMBO Journal

View full text Add to dashboard Cite

We have used transgenic mice to analyse the regulation of the bovine vasopressin (BVP) gene. We find that the restriction of BVP gene expression to anatomically and functionally distinct hypothalamic neuronal groups is achieved, in part, by selective repression. The expression of a 1.25 kb BVP proximal promoter, which on its own confers general expression of a reporter to most peripheral and brain tissues, was limited by sequences in the BVP structural gene to neural cells in the adrenal medulla and brain. Transgene expression in the hypothalamus was shown to be regulated by the physiological stimulus of dehydration in parallel with the endogenous gene. The expression of a larger 13.4 kb BVP transgene, containing 9 kb of 5′ upstream sequence, the VP structural gene and 1.5 kb 3′ of the transcription unit, was even more restricted and resembles that of the endogenous mouse gene. Hypothalamic expression of the 13.4 kb BVP transgene was regulated appropriately in response to an osmotic challenge.

show abstract

Chapter 7 Neuropeptide gene expression in transgenic animals

Cited by 7 publications

References 64 publications

In Vivo Gene Transfer Studies on the Regulation and Function of the Vasopressin and Oxytocin Genes

In Vivo Gene Transfer Studies on the Regulation and Function of the Vasopressin and Oxytocin Genes

Neurohormones: oxytocin, vasopressin and related peptides – structure, genes, receptors, and evolution

Neuron-specific expression and physiological regulation of bovine vasopressin transgenes in mice.

Contact Info

Product

Resources

About