TABLE 1.
Genes used in generating transgenic rodent lines for studying respiratory rhythm generation.
| Gene | Line | Type | Reference | Notes |
|---|---|---|---|---|
| Atp1a2 | Atp1a2−/− | CKO | Ikeda et al. (2004) | Brain-specific due to gene expression pattern |
| Atoh1 | Atho1 Cre∕− ; Tau mgfp−nLacZ | CKO | Huang et al. (2012) | Expression in hindbrain during development |
| Atho1 Phox2bCKO | CKO | Expression preferentially in retrotrapezoid nucleus | ||
| Atoh1 HoxA4CKO | CKO | Expression in caudally derived Atho1 lineages | ||
| chx10 | Chx10:LNL:DTA | CKO | Crone et al. (2012) | Ablation of V2a neurons by diphtheria toxin A-chain (DTA) |
| Dbx1 | Dbx1+/CreERT2; Rosa26 tdTomato | CKI | Wang et al. (2014) | Identification of Dbx1 neurons |
| GluR3 | GluR3−/− | KO | Steenland et al. (2008) | Constitutive knockout |
| Jmjd3 | Jmjd3−/− | KO | Burgold et al. (2012) | Neurogenic factor required for maintenance of the preBötC |
| Jmjd3−/−; Jmjd3 mut 21 | KO | Point mutation A1388H | ||
| Jmjd3−/−; Jmjd3 mut 65 | KO | Point mutation A1388H | ||
| Jmjd3−/−; Rosa26 Jmjd3 | KO/CKI | Conditional rescue of Jmjd3 | ||
| Rosa26 flSTOP−Jmjd3 | CKI | Conditional expression of Jmjd3 | ||
| Lbx1 | Lbx1 GFP∕GFP | KO | Pagliardini et al. (2008) | Expression during development of medulla and spinal cord |
| MAO-A | Tg8 | KO | Bou-Flores et al. (2000) | Deletion of gene. Displays excess of 5-HT. |
| Mafb | Mafb−/− | KO | Blanchi et al. (2003) | Constitutive knockout. Differentiation of hematopoietic system, podocytes, and specification of rhombomeres in the early hindbrain |
| Mecp2 | B6.129P2(C)-MeCP2 tm1−1Bird | KO | Mironov et al. (2009) ■ | Constitutive knockout. Transduction of neurons in organotypic slices with a Ca2+sensor (D3cpv) via AAV. |
| Rnx | Rnx−/− | KO | Shirasawa et al. (2000) | Orphan homeobox gene expressed in the developing dorsal and ventral region of the medulla |
| Sst | Sprague-Dawley | KI | Tan et al. (2008) ★ ■ | Transduction with AAV2-pA-Sst-alstR-IRES-EGFP or AAV2-pA-Sst-EGFP into the preBötC is performed to express the allatostatin receptor and EGFP (enhanced green fluorescent protein) in Sst neurons. Alternatively, only EGFP is expressed in Sst neurons using AAV2-pA-Sst-EGFP. |
| STIM1 | STIM1−/− | KO | Berry et al. (2003) | Highly expressed in the central nervous system and placenta |
| Thy1.2 | Thy1.2-EYFP | KI | Winter et al. (2007) | Expression of EYFP (enhanced yellow fluorescent protein) in the ventral respiratory column, preBötC, and the rostral ventral respiratory group neurons |
| Thy1.2-HcRed | KI | Expression of HcRed in the ventral respiratory column, preBötC, and the rostral ventral respiratory group neurons | ||
| Tshz3 | Tshz3+/lacZ | KO | Caubit et al. (2010) | Transcription factor expressed in the brainstem |
| Vglut2 | Vglut2 f/f;PCre | CKO | Wallén-Mackenzie et al. (2006) | First model showing complete uncompensated functional impairment of the respiratory CPG. |
| Vglut2, Dbx1, and Sst | Dbx1-tdTomato | CKI | Koizumi et al. (2016) | Expression of tdTomato in Dbx1-neurons |
| Dbx1-tdTomato-Arch-GFP | CKI | Expression of tdTomato, archaerhodopsin (Arch), and GFP in Dbx1-neurons | ||
| Sst-tdTomato | CKI | Expression of tdTomato in Sst-expressing neurons | ||
| SST-tdTomato-Arch-GFP | CKI | Expression of tdTomato, Arch, and GFP in Sst-expressing neurons | ||
| VgluT2-tdTomato | CKI | Expression of tdTomato in VgluT2-expressing neurons | ||
| VgluT2-tdTomato-Arch-GFP | CKI | Expression of tdTomato, Arch, and GFP in VgluT2-expressing neurons | ||
| VgluT2-tdTomato-Gad67-GFP | CKI | Expression of tdTomato in VgluT2-expressing neurons and expression of GFP in Gad67-expressing neurons | ||
| ZFHX | Zfhx4 PB/+ | KO | Zhang et al. (2021) | Transcriptional factor expressed in the brainstem |
Unless stated, all transgenic lines are from mice. ★Transgenic rats. ■Viral vectors. Atoh1/Math1 (Atonal BHLH, Transcription Factor 1), Atp1a2 (ATPase, Na+/K + Transporting Subunit Alpha 2), Chx10 (Visual system homeobox 2), Dbx1 (Developing Brain Homeobox 1), Gad67 (Glutamate Decarboxylase 67 KDa, Isoform), GluR3 (Glutamate Ionotropic Receptor AMPA, Type Subunit 3), Jmjd3 (Jumonji domain-containing protein-3), Lbx1 (Ladybird Homeobox 1), Mafb (MAF BZIP, Transcription Factor B), Maoa (Monoamine oxidase A), Mecp2 (Methyl-CpG, Binding Protein 2), Rnx (Respiratory Neuron Homeobox), Sst (Somatostatin), Stim1 (Stromal Interaction Molecule 1), Thy1 (Thy-1, cell surface antigen), Tshz3 (Teashirt Zinc Finger Homeobox 3), Vglut2 (Vesicular glutamate transporter 2), and Zfhx3 (Zinc Finger Homeobox 3).
KO, knockout; KI, knock-in; CKO, conditional knockout; CKI, conditional knock-in.