C3H/HeOuJ-Maoa^{Tg(H2-K1-Ifnb1)8Seif}/J

Stock number: 014132
Research areas: Developmental Biology Research, Neurobiology Research

Description

These H2-IFNB transgenic mice have the murine interferon beta 1 (Ifnb1) gene driven by a fragment of the histocompatibility 2, K1, K region (H2-K1) promoter. The transgene integrated into the X-linked monoamine oxidase A (Maoa) gene, replacing exons 2-3 and abolishing Maoa gene function. These mice may be useful for studying MAOA-related aggression and abnormal development of neural circuits under excess serotonin.

Detailed description

These H2-IFNB transgenic mice have the murine interferon beta 1 (Ifnb1) coding sequence driven by a fragment of the murine histocompatibility 2, K1, K region (H2-K1) promoter. The transgene integrated into the X-linked monoamine oxidase A (Maoa) gene, replacing exons 2-3 and abolishing Maoa gene function. Hemizygous males and homozygous females are viable, and fertile until at least 6 months. MAOA is a mitochondrial enzyme that oxidizes monoamine neurotransmitters and dietary monoamines. These mutants lack MAOA activity resulting in increased levels of serotonin, dopamine, and norepinephrine. Excess serotonin in these mice causes abnormal development of certain neural circuits, such as in the barrelfield. During the first two postnatal weeks, these mice successively exhibit increased trembling and head nodding, frantic running and falling over. Adult males exhibit increased aggression towards subordinate males, male intruders, and females during courtship. These changes are not attributable to expression of the Ifnb1 transgene. These mice may be useful for studying MAOA-related aggression and abnormal development of neural circuits under excess serotonin.

Development

The H2-IFNB transgene was designed with the murine interferon beta 1 (Ifnb1) gene driven by a histocompatibility 2, K1, K region (H2-K1) truncated promoter. The transgene was microinjected into fertilized C3H/HeOuJIco oocytes and mice from founder line 8 were bred to C3H/HeOuJIco mice. This transgene integrated into the X-linked monoamine oxidase A (Maoa) gene, replacing exons 2-3. These mice were backcrossed to C3H/HeOuJIco mice for at least 11 generations. Upon arrival at The Jackson Laboratory, transgenic mice were bred to C3H/HeOuJ inbred mice (Stock No. 000635) to establish the colony.

Allele

Symbol: Maoa^{Tg(H2-K1-Ifnb1)8Seif}
Name: transgene insertion 8, Isabelle Seif
MGI accession ID: MGI:2180818
Generation method: Transgenic
Attributes: Null/Knockout
Marker symbol: Maoa
Marker name: monoamine oxidase A
Chromosome: X
Strain of origin: C3H/HeOuJ
Expressed genes: Ifnb1,interferon beta 1, fibroblast,mouse, laboratory
Molecular note: Random integration of a transgene for IFN beta expressed under the control of a truncated H2-K1 promoter resulted in deletion of a 17 kb region encompassing exons 2 and 3 of the Maoa gene. Enzyme activity was absent in brain and spleen samples from mutant animals.