β-Actin: ubiquitously expressed cytoplasmic isoform of actin involved in cell structure, cell migration, and embryogenesis. See Gunning et al. (1987) PNAS, Sugiyama et. al (1988) Gene, and Quitschke et al. (1989) JBC.
CAG: Artificial construct pairing the chicken ß-actin/rabbit ß-globin hybrid promoter with the human cytomegalovirus enhancer element. Offers high-efficiency ubiquitous expression of transgenic proteins. See Belgian plasmid collection and Niwa et al. (1991) Gene.
CaMKIIα: Calcium-calmodulin kinase IIα, expression limited to neurons of the forebrain; low level expression starts by approx. E18 with maximal expression early postnatal and continuing throughout life.
DAT: Dopamine transporter expressed in ventral midbrain regions including the substantia nigra and ventral tegmental area. Regulates neurotransmission by transporting DA back into presynaptic terminals. See Augood et al (1993) Brain Res Mol Brain Res.
GAD2: Glutamic acid decarboxylase 2, gene encodes GAD65, which along with GAD1 encoding GAD67 is responsible for catalyzing production of GABA from L-glutamic acid (Erlander et al. (1991) Neuron). GAD65 protein is primarily found at the axon terminal and produces GABA for synaptic release, while GAD67 is located throughout the cytoplasm and produces GABA used in other processes (Kaufman et al. (1991) J Neurochem). GAD2 is expressed throughout development in GABAergic neurons and in certain non-neuronal cells. See Taniguchi et al. (2011) Neuron.
Grik4 (KA-1): Ionotropic glutamate receptor responsive to kainate. KA-1 expression is concentrated in the CA3 field of the hippocampus and in dentate gyrus, with lower levels found in other major glutamate-responsive regions such as the inner cortical layers and cerebellar Purkinje cells. See Wisden and Seeburg (1993) J Neurosci.
Nop: Neuropsin (aka Protease Serine 19 (Prss19) or Kallikrein-related peptidase 8 (Klk8)): wild-type Nop is normally expressed in the limbic system of the adult rodent brain, but due to insertion-site dependent effects, expression of TTA in Nop-TTA transgenic mice is limited to superficial layers II and III of medial entorhinal cortex, pre- and parasubiculum. See Yasuda and Mayford (2006) Neuron.
Pcp2: Purkinje cell protein 2 (aka L7 or GPSM4): Gα-interacting protein expressed specifically in Purkinje neurons of the cerebellum and ON bipolar cells in the retina of higher vertebrates. See Oberdick et al. (1988) Neuron, Vandaele et al. (1991) Genes Dev, Oberdick et al. (1996) J Comp Neurol.
POMC: proopiomelanocortin is endogenously expressed in the pituitary gland and in the arcuate nucleus of hypothalamus. Although endogenous POMC is absent in hippocampus, cryptic regions of the POMC promoter that are not required for arcuate and pituitary expression enable expression in immature granule neurons of the dentate gyrus (~ 2 weeks postmitotic) See Overstreet and Rubinstein (2004) J. Neurosci.
PrP: Prion protein promoter, ubiquitously expressed throughout brain and much of body starting at early embryonic ages and continuing throughout life. See Borchelt et al. (1996) Genet Anal.
ROSA26: Ubiquitously expressed locus discovered by retroviral gene trap. Expression is active from early embryonic stages (i.e. morula-blastocyst) through adult. Targeted alleles can be made homozygous without loss-of-function effects. See Soriano lab ROSA26 page and Zambrowicz et al. (1997) PNAS.
tetO: Tetracycline-responsive operator, artificial promoter used to drive expression of tetracycline-controlled transgenes, expressed only when tTA is present and tetracycline is not. See Lewandoski (2001) Nat Rev Genet. Currently 3 versions of this promoter exist, beginning with the original tetO described by Gossen and Bujard (1992) PNAS and progressing through the 2010 introduction of tetO-3G by Loew et al. (2010) BMC Biotechnol. See also Takara’s website for additional information on the latest promoters, historic evolution, and tetracycline transactivator variants.
Wfs1: Wolfram syndrome 1, encodes the endoplasmic reticulum membrane protein wolframin, involved in ER calcium regulation. Broadly expressed throughout the body, including liver, pancreas, retina, kidney, ovary and testis. Brain distribution is more limited: dorsal hippocampal CA1, caudal striatum (CPu), hypothalamus, nucleus accumbens (NAc) and superficial layers of the entorhinal cortex. See Luuk et al. (2008) JCN, Kawano et al. (2009) Neurosci. Res., Kitamura et al. (2014) Science.
APP: Amyloid precursor protein, one of only 3 genes associated with inherited autosomal-dominant AD Mutations named for the location of families in which they were identified, i.e. Swedish or Indiana.
Cre: DNA recombinase derived from P1 bacteriophage. Drives site-specific recombination at loxP or similar lox sites. Cre-mediated DNA cleavage between two lox sites results in excision, integration, inversion, or translocation of the intervening sequence depending on the initial orientation and position of the loxP sites. See Sternberg et. al (1981) J Mol Biol., Hoess et. al (1985) J Mol Biol., and García-Otín et. al (2006) Front Biosci.
CreERT2: Cytoplasm-localized fusion of the Cre-recombinase and the human estrogen receptor ligand-binding domain. Mutations in the ligand binding domain render the protein insensitive to endogenous estrogens, but retain sensitivity to synthetic antagonist 4-hydroxytamoxifen. On binding tamoxifen, the complex is translocated to the nucleus where cre activates recombination of loxP-flanked DNA. See Feil et al. (1997) BBRC.
Flp: DNA recombinase from Saccharomyces cerevisiae, catalyzes DNA rearrangement via site-specific cleavage and strand exchange at FRT sites. Similar to Cre, Flp-based recombination results in excision, integration, inversion, or translocation of the intervening DNA depending on the initial orientation of FRT sites. See Gates et al. (1988) PNAS, Dymecki et al. (1996) PNAS, and García-Otín et al. (2006) Front Biosci.
GlyCl: Human glycine-gated chloride channel, aka glycine receptor α1, engineered for neuronal silencing with point mutations F207A to reduce glycine sensitivity and A288G to increase ivermectin sensitivity. See Lynagh and Lynch (2010) JBC.
MAPT: Microtubule-associated protein tau, Axonally-localized microtuble stabilizing protein. Alternate splicing leads to 6 protein isoforms in human (containing 3- or 4-microtubule binding domain repeats) but just 3 isoforms in mice (all 4-repeat). Point mutations in MAPT are associated with autosomal dominant forms of fronto-temporal lobar degeneration and ALS. Transgene used in mice is commonly 4-repeat with P301 missense mutation.
PS1: Presenilin 1, One of 3 genes associated with inherited autosomal-dominant AD, serves as the catalytic subunit of γ-secretase. Mutations named for amino acid changes caused by DNA alterations, such as dE9: exon 9 deletion mutation
TTA: Tetracycline-responsive transactivator, an artificial transcription factor that activates expression from the tetO promoter. Binding of tetracycline to TTA prevents it from activating transcription, thus shutting down expression of the controlled transgene. See Urlinger et al. (2000) PNAS and Baron et al. (1997) Nucleic Acids Res. There are three current tet-off transactivators in use: the original TTA (Furth et al. 1994), TTA-2 (Urlinger et al. 2000), and the doxycycline-insensitive variant H100Y (Hecht et al. 1993). Each of these three bind to all versions of the tetO promoter.
Line 85 PrP-APPswe/PrP-PS1dE9 coinjected
Congenic C57BL/6J background: http://jaxmice.jax.org/strain/005864.html
Hybrid B6C3 background: http://jaxmice.jax.org/strain/004462.html
Original reference: Jankowsky et al. Hum Mol Genet 2004
Tetracycline-Controlled Transgenics – Driver Lines
Line B CaMKIIα-TTA
Congenic C57BL/6J background: http://jaxmice.jax.org/strain/007004.html
Hybrid B6/CBA background: http://jaxmice.jax.org/strain/003010.html
Original reference: Mayford et al. Science 1996
NOTE: This line expresses the original TTA published in Furth et al. 1994.
Line S EC Prss19 (Nop)-TTA
C57BL/6 n3+ backcross: Kind gift of Mark Mayford, Scripps Research Institute (also available through MMRRC: https://www.mmrrc.org/catalog/sds.php?mmrrc_id=31779)
Original reference: Yasuda and Mayford, Neuron 2006
NOTE: This line expresses the second-generation TTA-2 published in Urlinger et al. 2000.
Line ROSA26:LNL:TTA (converts Cre to TTA)
Congenic C57BL/6J background: http://jaxmice.jax.org/strain/011008.html
Original reference: Wang et al., Neurobiol. Dis. 2008
NOTE: This line expresses a modified version of TTA (mTTA).
Line 3 Pcp2-TTA
Mixed FVB/N; SW outbred background shared by Dr. Roy Sillitoe, BCM
Congenic FVB/N background: http://jaxmice.jax.org/strain/005625.html
Original reference: Zu et al. J Neurosci 2004
NOTE: This line expresses the original TTA published in Furth et al. 1994.
Tetracycline-Controlled Transgenics – Responder Lines
Line nls-lac-CMK tetO-GFP-nls-LacZ-CaMKIIα 3’ UTR
C57BL/6 backcross: Kind gift of Mark Mayford, Scripps Research Institute
Original reference: Mayford et al. PNAS 1996
Cre, CreER, and Flp Transgenics – Driver Lines
GAD2-Cre (IRES knock-in)
NOTE: IRES-Cre insertion to 3' UTR of GAD2, impact on GAD2 expression not yet evaluated
Congenic C57BL/6N background: https://www.jax.org/strain/019022
Original reference: Taniguichi et al., Neuron 2011
Wfs1-Cre (BAC transgenic)
C57BL/6 background: kind gift of Susumu Tonegawa, MIT
Original reference: Kitamura et al. Science 2014