Transgenic & Recombinant Mice

Transgenic Mice

The Institute for Behavioral Genetics has the world's most complete collection of mouse strains that have been engineered to express mutations in nicotinic cholinergic receptor (nAChR) subunit genes. These strains are grouped below by type of mutation. Genotyping protocols are linked to the gene name or mutation in the second column. Literature referencing work done with mice supported by this grant is available on pubmed.  Maintenance is supported by a P30 grant from NIDA, and these strains are available as heterozygous breeding triads to university researchers at minimal cost.  For more information on obtaining null mutant and transgenic mice contact Jerry Stitzel.

• Null Mutations
• Fluorescent Tags
• Point Mutations
• Congenic Lines

Recombinant Inbred Mice

Please see below for more information on LXS RI mouse strains

Genetic structure of the LXS panel of recombinant inbred mouse strains: a powerful resource for complex trait analysis.

Null Mutations

We have breeding colonies of null mutants (gene knockouts) for eight of the eleven known mammalian neuronal nAChR subunit genes. Some of the null mutations have been bred onto more than one genetic background by congenic breeding for a minimum of seven generations. All of these strains were provided to IBG by investigators at other universities, which are listed in the “Source” column. These null mutants have been investigated with a number of useful radiolabeled nicotinic ligands and in situ hybridization techniques, the images of which can be observed by clicking on the respective nAChR subunits. Comparisons of the in situ hybridizations can be seen here.

Fluorescent Tags

Another useful tool for tracking the distribution of nicotinic receptors containing particular subunits is fluorescent tags. The sequence for the desired fluorescent label, GFP, YFP or mCherry, is inserted in the portion of the Chrna coding for the intracellular loop of the receptor subunit in question. All of these mice were developed by Henry Lester’s Lab at Cal Tech on a mixed background of 129S6/SvEv and C57BL/6. The following papers provide a detailed description of the development of the a4 YFP plasmid and the B3 and a6 GFP plasmids.

Point Mutations

Several mice have been developed based on research into a number of different human conditions and associated predisposition for nicotine dependence. Two of these have been engineered to expressed human genes that cause autosomal dominant frontal lobe elilepsy (ADNFLE). These are both “gain of function” mutations and there is one each in the a4 (S6’F) and B2 (V10’L) subunits. Another gain of function mutant in the a4 (L9’S) could be useful for studying these types of disorders, although there is no known expression of this particular mutation in humans. Last, the Stitzel lab has engineered the a5 rs16969968 (D398N) mouse line based on a human polymorphism which has been identified by numerous Genome Wide Association Studies with a number of smoking behaviors.

Congenic Lines

We identified allelic variation in the mouse α5 and α7 genes (Chrna5 and Chrna7) between two inbred mouse strains (C3H and DBA/2). Traditional backcross breeding strategies were used to generate reciprocal congenic lines in which the DBA/2 allele of Chrna5 or Chrna7 has been introgressed onto a C3H genetic background (referred to as C3.D2Chrna5 or C3.D2Chrna7) and vice versa (referred to as D2.C3Chrna5 or D2.C3Chrna7). Genetically, these congenic lines are approximately 99% C3H or DBA/2 but carry the opposite strain's Chrna5 or Chrna7 locus (plus flanking genes).