Transgenic mice with altered levels of galanin/galanin receptor expression
| Galanin/Galanin Receptor Overexpressing Transgenic Mice | |
|---|---|
| Promoter/DNA/Strain | Phenotype |
| Dopamine β-hydroxylase (Mazarati et al., 2000)/Human DBH (5.8 kb) driving 4.6 kb mouse genomic preprogalanin (10.4 kb transgene)/C57BL/6J | Increased thresholds to noxious heat intact (Blakeman et al., 2001) |
| Decreased neuropathic pain and shorter duration (Hygge-Blakeman et al., 2004) | |
| Reduced spinal excitability following c-fiber stimulation (Grass et al., 2003a) | |
| Galanin overexpression in neurons containing adrenaline or NA. Decrease in number of cholinergic neurons in the horizontal limbs of the diagonal band (Steiner et al., 2001) | |
| Increase in GAL1 in specific brain regions (Hohmann et al., 2003a) | |
| Increased threshold for induction of after discharge (Mazarati et al., 2000) | |
| No difference in neuroendocrine profile (Hohmann et al., 2003b) | |
| Increased NA and 5-HT release after forced swim (learned helplessness—increase in depressive behavior) (Yoshitake et al., 2004) | |
| Reduced ACh release in the ventral hippocampus (Laplante et al., 2004) | |
| Decrease in opiate withdrawal behavior (Zachariou et al., 2003) | |
| Deficits in olfactory memory (Wrenn et al., 2003) | |
| Impaired response to trace cued fear conditioning (Kinney et al., 2002) | |
| Galanin (Bacon et al., 2002)/20 kb murine genomic galanin upstream of the galanin gene/CBA/BL6 F1 hybrid | No difference in intact mechanical thresholds but higher after nerve injury, returned to intact values by day 7 (Bacon et al., 2007; Hulse et al., 2011) |
| Reduction in acetone-induced pain-like behavior after PSNI (Hulse et al., 2012) | |
| Lower levels of cell death in vivo and in vitro (Elliott-Hunt et al., 2004) | |
| Decrease in opiate withdrawal behavior (Holmes et al., 2012) | |
| Galanin (inducible) (Pope et al., 2010)/tTA under control of 20 kb murine genomic galanin, 4.6 kb murine genomic galanin under control of tetO/CBA/BL6 F1 hybrid | Increased mechanical thresholds after nerve injury reduced by galanin suppression (Pope et al., 2010) |
| Growth hormone (Perumal and Vrontakis, 2003)/320 bp rat GH promoter driving full-length rat preprogalanin cDNA including poly A tail (4.5 kb transgene)/C57BL6/SJL F2 × Swiss CD | Increased serum levels of galanin, prolactin and GH (GH in males only) |
| Pituitary hyperplasia and adenomas in older mice (Perumal and Vrontakis, 2003) | |
| Reduced CPZ-induced myelin breakdown (Zhang et al., 2012) | |
| Platelet-derived growth factor driving galanin (Holmberg et al., 2005a)/1.3 kb PDGF-β with galanin/GMAP gene construct, including intron 2 of the mouse galanin gene (genomic DNA and cDNA)/CBA/BL6 F1 hybrid | Increase in learned helplessness in old mice (Pirondi et al., 2005b). Increase in learned helplessness (Kuteeva et al., 2005) |
| Reduced neuronal loss postaxotomy, 35% reduction in plasma extravasation, increased response in phase 2 of formalin test (Holmberg et al., 2005a) | |
| Elevated thermal thresholds but no difference in mechanical thresholds or cold thermal in intact adults (Blakeman et al., 2001) | |
| Decreased response to evoked seizures (Kokaia et al., 2001) | |
| Delayed reduction in NA after intracerebroventricular injection of galanin to ventral hippocampus. Increased NA and 5-HT release following forced swimming stress (Kehr et al., 2001) | |
| Platelet-derived growth factor driving GAL2 (Le Maitre et al., 2011)/1.3 kb PDGF-β driving mouse genomic GAL2 with EGFP | Decreased immobility during the forced swim test (Le Maitre et al., 2011) |
| Prolactin (Cai et al., 1999)/2.5 kb rat prolactin promoter driving 4.6 kb murine genomic galanin (part of the first noncoding exon and all five coding exons for preprogalanin)/7.1 kb transgene/No details on strain | Increased prolactin synthesis and pituitary hyperplasia in older females (Cai et al., 1999). No increase in prolactin or hyperplasia in males. |
| Ret (Holmes et al., 2003)/12 kb murine c-ret cDNA driving 4.6 kb murine genomic galanin promoter (upstream of galanin gene)/CBA/BL6 F1 hybrid | Elevated thermal and mechanical thresholds in intact mice and after injury (Holmes et al., 2003) |
| Reporters and Cre-expressing line | |
| Gal5.1-hßg-lacZ (Davidson et al., 2011)/5.1 kb human genomic galanin found 42 kb upstream of the galanin transcriptional start site with human β-globulin promoter and β-galactosidase reporter gene/CBA/BL6 F1 hybrid | Directed expression in galaninergic neurons of the PVN, ARC, and amygdala (Davidson et al., 2011) |
| 20 kb Gal-lacZ (Bacon et al., 2007)/20 kb murine genomic galanin upstream of the GAL gene with 3.5 kb β-galactosidase reporter gene/CBA/BL6 F1 hybrid | Identical axotomy response to endogenous galanin in DRG neurons and in the developing DRG at embryonic day 17 (Bacon et al., 2007) |
| 4.6 kb Gal-lacZ (Bacon et al., 2007)/4.6 kb murine genomic galanin upstream of the galanin gene with 3.5 kb β-galactosidase reporter gene/CBA/BL6 F1 hybrid | Identical to 20 kb Gal-lacZ (Bacon et al., 2007) |
| 1.9 kb Gal-lacZ (Bacon et al., 2007)/1.9 kb murine genomic galanin upstream of the galanin gene with 3.5 kb β-galactosidase reporter gene/CBA/BL6 F1 hybrid | Loss of embryonic and intact adult DRG expression and axotomy response (Bacon et al., 2007) |
| 4.6 Δ23,18 kb Gal-lacZ (Bacon et al., 2007)/4.6 kb murine genomic galanin upstream of the galanin gene but with deletion of the 23 bp 5′ putative Stat/Smad (−4326 to −4304) and 18 bp Stat/Smad/Ets (−2551 to −2534) binding sites, with 3.5 kb β-galactosidase reporter gene/CBA/BL6 F1 hybrid | No effect on embryonic or adult DRG expression but loss of axotomy response (Bacon et al., 2007) |
| GAL-Cre (Wu et al., 2014)/C56BL/6J | Use of galanin-Cre line to demonstrate that galanin neurons in the medial preoptic area govern parental behavior |
| GAL2-OE-EGFP (Le Maitre et al., 2011) | High levels of GAL2 expression in the presubiculum, subiculum, cingulate cortex, retrosplenial granular and agranular cortices, subregions of the prefrontal cortex and the olfactory bulb (Le Maitre et al., 2011) |
| Knockouts | |
| Galanin (Wynick et al., 1993)/129OlaHsd | Reduced intact thermal and mechanical pain thresholds. Reduced mechanical allodynia after nerve injury (Kerr et al., 2000a; Holmes et al., 2003) |
| Increase in apoptosis in DRG at postnatal day 3–4 with reduction in number of small peptidergic neurons. Decreased regeneration in vivo and in vitro (Holmes et al., 2000; Sachs et al., 2007) | |
| Loss of one-third of cholinergic neurons in basal forebrain (O'Meara et al., 2000) | |
| Deficits in evoked ACh release (O'Meara et al., 2000; Kehr et al., 2001) and loss of spatial memory in aged mice (O'Meara et al., 2000; Massey et al., 2003) | |
| Increase in hippocampal cell death in vivo and in vitro (Elliott-Hunt et al., 2004, 2011) | |
| Increase in induced seizures (Mazarati et al., 2000) | |
| Marked reduction in levels of prolactin in the anterior pituitary and in plasma (Wynick et al., 1998) | |
| Decreased severity of cerulein-induced acute pancreatitis (Bhandari et al., 2010b) | |
| Reduced insulin secretion in response to non-neuronal stimulation and impaired glucose elimination (Ahren et al., 2004) | |
| Decreased food consumption on high-fat diet (Adams et al., 2008; Karatayev et al., 2010) Decreased ethanol intake and preference in female mice. Decreased orexin and melanin-concentrating hormone in the perifornical lateral hypothalamus (Karatayev et al., 2010) | |
| Increase in opiate withdrawal behavior (Zachariou et al., 2003) | |
| Decreased sensitivity to nicotine and no increase in ERK2 activation in mice that showed nicotine conditioned place preference (increase in WT) (Neugebauer et al., 2011) | |
| Increase in secreting sweat glands following thermal stimulation (Vilches et al., 2012) | |
| GAL1 (Jacoby et al., 2002)/C57BL/6J and 129T2/SvEmsJ | Increased sensitivity to both heat and cold intact. Increased duration of pain-like behavior after nerve injury (Blakeman et al., 2003) |
| No difference in mechanical or thermal thresholds in intact animals but increased hyperalgesia after thermal injury and faster recovery after spinal nerve ligation (Malkmus et al., 2005) | |
| No difference in regeneration in vivo (Blakeman et al., 2003) or in vivo (Blakeman et al., 2003; Mahoney et al., 2003a) | |
| Increase in opiate withdrawal behavior (Holmes et al., 2012) | |
| Spontaneous seizures and reduced plasma levels of IGF-1. No sex difference but strain difference in seizures; not present in mice on 129/Sv background (Jacoby et al., 2002) | |
| Impaired response to trace cued fear conditioning (Wrenn et al., 2004) | |
| Mild glucose intolerance after feeding and impaired glucose elimination. Increased food intake on high-fat diet (Zorrilla et al., 2007) | |
| No inhibition of vagal activity after stimulation of the vagus nerve and administration of galanin, as seen in WT and galanin-KO. No inhibition of vagal activity after stimulation of the vagus nerve in the presence of propranolol and administration of an NPY Y2 antagonist, as seen in WT and galanin-KO (Smith-White et al., 2003) | |
| GAL1 (Matkowskyj et al., 2000)/C57BL/6J | Decreased fluid secretion in the GI tract after infection with enteric pathogens (Matkowskyj et al., 2000) |
| No different from WT in response to Salmonella typhimurium infection (Matkowskyj et al., 2009) | |
| Decreased diarrhea after infection with rhesus rotavirus (Hempson et al., 2010a) | |
| GAL1/Deltagen (San Carlos, CA)/129P2/OlaHsd × C57BL/6 GAL2/Lexicon Genetics (The Woodlands, TX)/129/SvEvBrd × C57BL/6 | Increased neuronal loss in hippocampus after kainic acid administration (Schauwecker, 2010) |
| 15% less CGRP-IR neurons in DRG. No difference in thermal or mechanical thresholds in intact animals, but decreased response to neuropathic pain (no allodynia) and inflammatory pain (phase 2 of formalin test). Decrease of one-third in neurite outgrowth, decrease in phosphorylated ERK, increase in phosphorylated AKT (Hobson et al., 2006) | |
| Increased hippocampal cell death in vivo after glutamate treatment (Elliott-Hunt et al., 2011) | |
| Reduced levels of ERK and AKT after glutamate damage in vivo (Elliott-Hunt et al., 2007) | |
| GAL2/Deltagen (San Carlos, CA)/129 ⁄ Sv × C57BL/6 | 16–20% fewer neurons in DRG 7 days postaxotomy both intact and contralateral, no further loss ipsilateral (WT decrease of 26%). No difference in thermal or mechanical thresholds in intact animals or in hyperalgesia after injury (Shi et al., 2006) |
| Persistent escape deficits after inescapable shock (persistent depressive-like phenotype) (Lu et al., 2008) | |
| Galanin had no effect on GABAergic IPSPs in CeA neurons (decreased in WT) (Bajo et al., 2012) | |
| GAL2/Nura Inc. (Seattle, WA)/129S1/SvImJ | No difference in motor and sensory function, reproduction, feeding behavior, mood, learning and memory, or susceptibility to seizures (Gottsch et al., 2005) |
| Increased anxiety-like behavior in elevated plus-maze (Bailey et al., 2007) | |
| GAL3/Lexicon Genetics (The Woodlands, TX)/C57BL/6J | Increased cholesterol and triglyceride levels in homozygous males (Lexicon Genetics) (https://beta.infrafrontier.eu/sites/infrafrontier.eu/files/upload/public/lexicon/combined_lexicon_data/LEXKO-230-treeFrame.html) |
| Anxiety phenotype but no depression-like behavior (Brunner et al., 2014) | |
| Double GAL1 × GAL2-KO (Jacoby et al., 2002) × Deltagen (San Carlos, CA)/C57BL/6J × (129 ⁄ Svx C57BL/6) | Galanin had no effect on GABAergic IPSPs in CeA neurons (decreased in WT) (Bajo et al., 2012) |
ACh, acetylcholine; bp, base pairs; CGRP, calcitonin gene-related peptide; CPZ, cuprizone; DBH, dopamine β-hydroxylase; EGFP, green fluorescent protein; GH, growth hormone; GI, gastrointestinal; Hβg, human β-globulin; IGF, insulin-like growth factor; lacZ, β-galactosidase; PDGF, platelet-derived growth factor; PSNI, partial saphenous nerve ligation injury; PVN, paraventricular nucleus of the hypothalamus; SNL, spinal nerve ligation.