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. We have breeding colonies of null mutants (gene knockouts) for eight of the nine known neuronal nAChR subunit genes, two "gain of function" α4 mutant strains, and two strains that have been engineered to express human genes that cause autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). 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 us by investigators at other universities.

We have also developed two α5 congenic lines (strains) and two α7 congenic lines using marker-assisted breeding techniques. These congenic lines are useful for evaluating the phenotypic effects of naturally occurring polymorphisms in mouse nAChR genes. We identified allelic variation in the mouse α5 and α7 genes (Chrna5 and Chrna7) between two inbred mouse strains (C3H and DBA/2) using restriction fragment length polymorphism analysis. 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).

Faculty:

• Al Collins
• Jerry Stitzel

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