Errijgers V, Van Dam D, Gantois I, Van Ginneken C J, Grossman A W, D'Hooge R, De Deyn P P, Kooy R F
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Genes Brain Behav. 2007 Aug;6(6):552-7. doi: 10.1111/j.1601-183X.2006.00282.x. Epub 2006 Nov 3.
Mice of the FVB/N strain are severely visual impaired as a result of tyrosinase gene defects, leading to a deficiency of the key enzyme for melanin synthesis in skin and eye and of cyclic guanosine monophosphate phosphodiesterase gene defects, which results in albinism (Tyr(c/c)) and retinal degeneration (Pde6b(rd1/rd1)), respectively. Nevertheless, FVB/N mice are commonly used for the generation of transgenic animals because of their large, strong pronuclei and high breeding performance. However, due to visual impairment of the FVB/N animals, the resulting transgenic animals cannot be used in tests that depend on vision, including tests of cognitive behavior. Therefore, we have bred a sighted version of the FVB/N strain by an outcross between FVB/N and 129P2/OlaHsd, followed by repeated backcrosses to FVB/N mice while selecting against albinism and homozygosity of the retinal degeneration mutation. After 11 generations of backcrossing, sighted animals were intercrossed to generate the congenic FVB.129P2-Pde6b(+) Tyr(c-ch)/Ant strain, which is pigmented (Tyr(c-ch)/(c-ch)) and devoid of the genetic predisposition to retinal degeneration. The accurate visual abilities of the FVB.129P2-Pde6b(+) Tyr(c-ch)/Ant mice, for which we propose the name FVBS/Ant, demonstrated a clear visual evoked potential in the presence of normal eye histology and improved performance in the Morris water maze test.
FVB/N品系的小鼠由于酪氨酸酶基因缺陷而严重视力受损,导致皮肤和眼睛中黑色素合成的关键酶缺乏,以及环磷酸鸟苷磷酸二酯酶基因缺陷,分别导致白化病(Tyr(c/c))和视网膜变性(Pde6b(rd1/rd1))。然而,FVB/N小鼠因其大而强壮的原核和高繁殖性能,常用于转基因动物的培育。然而,由于FVB/N动物的视力受损,所产生的转基因动物不能用于依赖视觉的测试,包括认知行为测试。因此,我们通过将FVB/N与129P2/OlaHsd进行远交,随后反复回交至FVB/N小鼠,同时选择对抗白化病和视网膜变性突变的纯合性,培育出了FVB/N品系的有视力版本。经过11代回交后,将有视力的动物进行互交,以产生同基因的FVB.129P2-Pde6b(+) Tyr(c-ch)/Ant品系,该品系有色素沉着(Tyr(c-ch)/(c-ch))且没有视网膜变性的遗传易感性。我们提议将其命名为FVBS/Ant的FVB.129P2-Pde6b(+) Tyr(c-ch)/Ant小鼠的准确视觉能力,在正常眼组织学情况下表现出明显的视觉诱发电位,并且在莫里斯水迷宫测试中的表现有所改善。