Structure-function relationships of ion channels; Gene Discovery Project

Influenza Virus Ion Channel
Influenza continues to kill more people in the developed world than AIDS. There are only two inhibitors of the virus that work for people who are already infected, and one of them, amantadine, works by inhibiting the ion channel contained in the virus particle. We study this ion channel because of its importance in the virus and because it serves as a simple model of ion channels in general.

Gene Discovery Project
By mutagenizing mice and screening them for specific functional defects, scientists have been able to discover genes that are involved in the various important biological processes and to create models for important human diseases. An example of one important process is the circadian clock, and the essential Clock gene of the mouse was discovered in our department using this approach. My lab is using this process to identify mutations affecting blindness and asthma.

e-mail Dr. Pinto
ph: 847.491.7915
fax: 847.491.5211

• Maddox DM, Vessey KA, Yarbrough GL, Invergo BM, Cantrell DR, Inayat S, Balannik V, Hicks WL, Hawes NL, Byers S, Smith RS, Hurd R, Howell D, Gregg RG, Chang B, Naggert JK, Troy JB, Pinto LH, Nishina PM, McCall MA. (2008). Allelic variance between GRM6 mutants, Grm6nob3 and Grm6nob4 results in differences in retinal ganglion cell visual responses. J Physiol. 586 (Pt 18): 4409-24. [Full Text]

• Jing X, Ma C, Ohigashi Y, Oliveira FA, Jardetzky TS, Pinto LH, Lamb RA. (2008). Functional studies indicate amantadine binds to the pore of the influenza A virus M2 proton-selective ion channel. PNAS U S A. 105(31): 10967-72.

• Stouffer AL, Ma C, Cristian L, Ohigashi Y, Lamb RA, Lear JD, Pinto LH, DeGrado WF. (2008). The interplay of functional tuning, drug resistance, and thermodynamic stability in the evolution of the M2 proton channel from the influenza A virus. Structure. 16(7):1067-76.[Full Text]

• Ma C, Soto CS, Ohigashi Y, Taylor A, Bournas V, Glawe B, Udo MK, Degrado WF, Lamb RA, Pinto LH. (2008). Identification of the pore-lining residues of the BM2 ion channel protein of influenza B virus. J Biol Chem. 283(23):15921-31.

• Pinto LH, Eaton E, Chen B, Fleisher J, Shuster D, McCauley J, Kedainis D, Siepka SM, Shimomura K, Song EJ, Husain A, Lakser OJ, Mitchell RW, Dowell ML, Brown M, Camoretti-Mercado B, Naclerio R, Sperling AI, Levin SI, Turek FW, Solway J. (2008). Gene-environment interactions in a mutant mouse kindred with native airway constrictor hyperresponsiveness. Mamm Genome. 19(1):2-14.

• Balannik V, Lamb RA, Pinto LH. (2008). The oligomeric state of the active BM2 ion channel protein of influenza B virus. J Biol Chem. 283(8):4895-904.

• Pinto LH, Invergo B, Shimomura K, Takahashi JS, Troy JB. (2007). Interpretation of the mouse electroretinogram. Doc Ophthalmol. 115(3):127-36.

• Pinto LH, Vitaterna MH, Shimomura K, Siepka SM, Balannik V, McDearmon EL, Omura C, Lumayag S, Invergo BM, Glawe B, Cantrell DR, Inayat S, Olvera MA, Vessey KA, McCall MA, Maddox D, Morgans CW, Young B, Pletcher MT, Mullins RF, Troy JB, Takahashi JS. (2007). Generation, identification and functional characterization of the nob4 mutation of Grm6 in the mouse. Vis Neurosci. 24(1):111-23.

• Pinto LH, Invergo B, Shimomura K, Takahashi JS, Troy JB. (2007). Interpretation of the mouse electroretinogram. Doc Ophthalmol. 115(3):127-36.

• Johnson BA, Ikeda S, Pinto LH, Ikeda A. (2006). Reduced synaptic vesicle density and aberrant synaptic localization caused by a splice site mutation in the Rs1h gene. Vis Neurosci. 23(6):887-98.

• Pinto LH, Lamb RA. (2007). Controlling influenza virus replication by inhibiting its proton channel. Mol Biosyst. 3(1):18-23.

• Pinto LH, Lamb RA. (2006). Influenza virus proton channels. Photochem Photobiol Sci. 5(6):629-32.

• Vitaterna MH, Pinto LH, Takahashi JS. (2006). Large-scale mutagenesis and phenotypic screens for the nervous system and behavior in mice.
Trends Neurosci. 29(4):233-40. 

• Chen B, Liu G, Shardonofsky F, Dowell M, Lakser O, Mitchell RW, Fredberg JJ, Pinto LH, Solway J. (2006). Tidal breathing pattern differentially antagonizes bronchoconstriction in C57BL/6J vs. A/J mice.
J Appl Physiol. 101(1):249-55.

• Pinto LH, Lamb RA. (2006). The M2 proton channels of influenza A and B viruses. J Biol Chem. 281(14):8997-9000.

• Pinto LH, Vitaterna MH, Shimomura K, Siepka SM, McDearmon EL, Fenner D, Lumayag SL, Omura C, Andrews AW, Baker M, Invergo BM, Olvera MA, Heffron E, Mullins RF, Sheffield VC, Stone EM, Takahashi JS. (2005). Generation, characterization, and molecular cloning of the Noerg-1 mutation of rhodopsin in the mouse. Vis Neurosci. 22(5):619-29.

• Venkataraman P, Lamb RA, Pinto LH. (2005). Chemical rescue of histidine selectivity filter mutants of the M2 ion channel of influenza A virus. J Biol Chem. 280(22):21463-72.

• Pinto LH, Vitaterna MH, Siepka SM, Shimomura K, Lumayag S, Baker M, Fenner D, Mullins RF, Sheffield VC, Stone EM, Heffron E, Takahashi JS. (2004). Results from screening over 9000 mutation-bearing mice for defects in the electroretinogram and appearance of the fundus. Vision Res. 44(28):3335-45.

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