Sex-linked behavioural differences in mice expressing a human insulin transgene in the medial habenula

Douhet, Philippe; Bertaina, Valérie; Durkin, Thomas; Calas, A.; Destrade, Claude

doi:10.1016/s0166-4328(97)00071-5

Cited by 8 publications

(4 citation statements)

References 38 publications

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“…At a mechanistic level, there are several precedents in non-DAergic systems for gender-specific expression of mutant phenotypes at the level of behavior, for example mice expressing the D-168 human insulin transgene (Douhet et al, 1997), or lacking the Mas proto-oncogene (Walther et al, 2000) or the gene encoding phosphodiesterase 1B (Reed et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Topographical Assessment of Ethological and Dopamine Receptor Agonist-Induced Behavioral Phenotype in Mutants with Congenic DARPP-32 ‘Knockout’

Nally

McNamara

Clifford

et al. 2003

Neuropsychopharmacol

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Congenic (10 backcrosses into C57BL/6J) mutants with targeted gene deletion of DARPP-32, a neuronal phosphoprotein regarded as an essential mediator of the biological effects of dopamine (DA), were assessed phenotypically using an ethologically based approach that resolves all topographies of behavior in the mouse repertoire. Over initial exploration, female, but not male, DARPP-32 mutants evidenced increased locomotion and decreased grooming, while a decrease in rearing seated was evident in mutants of both genders; continuing assessment over several hours did not reveal additional phenotypic effects. Following challenge with the nonselective DA receptor agonist apomorphine, low doses were associated with reduced levels of sniffing, grooming, total rearing, and rearing seated in DARPP-32 mutants relative to wildtypes; this would suggest some role for DARPP-32 in mediating the biological effects of presynaptic D 2 -like autoreceptor or inhibitory postsynaptic D 2 -like receptor activation. Following challenge with higher doses, while stereotyped sniffing and locomotion with chewing was largely unaltered, the additional murine response of Straub tail was essentially abolished in DARPP-32 mutants, indicating some specific involvement of DARPP-32 in mediating this topography of behavior; additionally, there were overall reductions in levels of sniffing, total rearing, rearing seated, and grooming in DARPP-32 mutants that were unrelated to the dose of apomorphine administered, indicating broader topographical effects following the stress of the injection procedure relative to more naturalistic conditions. The developmental absence of DARPP-32 following targeted gene deletion appears to be associated with compensatory processes that maintain certain topographies of spontaneous and agonist-induced DAergic function, while other topographies remain impaired.

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Section: Discussionmentioning

confidence: 99%

Topographical Assessment of Ethological and Dopamine Receptor Agonist-Induced Behavioral Phenotype in Mutants with Congenic DARPP-32 ‘Knockout’

Nally

McNamara

Clifford

et al. 2003

Neuropsychopharmacol

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“…Sex differences should be considered as males and females may be differentially affected by gene mutations. For example, male and female ddY mice differ in the performance of spatial learning tasks but not in avoidance learning (Mishima et al 1986), and delta-168 transgenic mice show sex-linked changes in locomotor activity and learning (Douhet et al 1997). Genotype-by-sex interactions also have been found in tests of anxiety in 5-HT1A receptor knockout mice (Ramboz et al 1998).…”

Section: Procedural Questions For Designing Behavioral Studiesmentioning

confidence: 99%

Developing Standardized Behavioral Tests for Knockout and Mutant Mice

Brown

Stanford²,

Schellinck³

2000

ILAR Journal

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“…Their classical role in energy (glucose) metabolism has now been extended to include many behavioural functions, such as food intake, motor activity, and memory ( Mayer et al . 1990 ; Douhet et al . 1997 ; Wickelgreen 1998).…”

Section: Introductionmentioning

confidence: 99%

“…Insulin or insulin-related peptides are found in both vertebrates and invertebrates (Smit et al 1998). Their classical role in energy (glucose) metabolism has now been extended to include many behavioural functions, such as food intake, motor activity, and memory (Mayer et al 1990;Douhet et al 1997;Wickelgreen 1998). The existence of insulin receptors in the brain (Pezzino et al 1996;DoreÂ et al 1997) and the transport of insulin across the blood±brain barrier may explain these behavioural effects.…”

Section: Introductionmentioning

confidence: 99%

Human insulin gene insertion in mice. Effects on the sleep–wake cycle?

Valatx

Douhet

Bucchini

1999

Journal of Sleep Research

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Recently, insulin synthesis and the presence of an insulin receptor have been demonstrated in the brain. Intracerebroventricular infusion of insulin causes a selective increase in the amount of slow-wave sleep. In the present study, the sleep-wake cycle of transgenic mice, with or without habenular neuronal expression of the human insulin gene, was studied to investigate the possible role of brain insulin as a sleep modulator. Slow-wave sleep duration was increased in those mice expressing human insulin in the habenula. However, it is possible that this effect was not due to expression of the insulin transgene, but to the genetic background of one of the parental strains (CBA) used for insertion of the transgene. Users of transgenic mice should be aware of this possibility and be cautious in interpreting results when hybrid embryos are used as transgene recipients.

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Sex-linked behavioural differences in mice expressing a human insulin transgene in the medial habenula

Cited by 8 publications

References 38 publications

Topographical Assessment of Ethological and Dopamine Receptor Agonist-Induced Behavioral Phenotype in Mutants with Congenic DARPP-32 ‘Knockout’

Topographical Assessment of Ethological and Dopamine Receptor Agonist-Induced Behavioral Phenotype in Mutants with Congenic DARPP-32 ‘Knockout’

Developing Standardized Behavioral Tests for Knockout and Mutant Mice

Human insulin gene insertion in mice. Effects on the sleep–wake cycle?

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