SdyDBA and sdyBL6 mice

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As noted above, the original sdy mice were Dtnbpl mutants of the DBA/2J strain. This strain, unlike C57BL/6 mice, is homozygous for six mutations related to neurological, melanogenic, and/or inflammatory disorders as documented by Cox et al. (2009) and Talbot et al. (2009). These include cadherin 23ahl (Cdh23ahl=Cdh753A) associated with an age-related hearing loss, as well as glycoprotein (transmembrane) nmbR150X (GpnmbR150X) and tyrosinase-related protein 1isa (Tyrp1isa) associated with pigmentary glaucoma. These mutations must be present in sdy mice derived from DBA/2J animals (i.e., sdy/DBA mice), though not all such mice are necessarily homozygous for them since some have wild-type Gpnmb (Anderson et al., 2002).

These various mutations in DBA/2J mice appear to account for several developmental abnormalities in such animals compared to C57BL/6 mice as discussed elsewhere (Talbot et al., 2009). DBA/2J mice develop a high-frequency hearing loss between 3 and 4 weeks of age. By 5 weeks, hearing loss is detected at all frequencies tested and persists through old age. Between 3 and 4 months, at least some DBA/2J mice begin showing symptoms of glaucoma. As early as 6-7 months, DBA/2J mice have abnormal irises. Since sdy/DBA mice are necessarily homozygous for most of the alleles causing these conditions, they must share most of the auditory and visual deficits developing in DBA/2J animals. They are also expected to share the enhanced responses of DBA/2J mice to stress and decreased responses to dopamine agonists, as well as cognitive deficits on auditory, olfactory, and visual tasks of DBA/2J compared to C57BL/6 mice.

To avoid the confounding variables presented by the DBA/2J mutations affecting brain function, several groups have transferred the Dtnbp1sdy mutation onto a C57BL/6J genetic background to create sdy/BL6 mice. These are not commercially available, but can be generated from sdy/DBA animals recovered from cryopreserved embryos (stock 001594 at the Jackson Laboratory [Bar Harbor, ME]). On both the DBA/2J and C57BL/ 6J backgrounds, sdy mice are fully viable and appear normal in many respects apart from depigmentation of hair and eyes. Both heterozygous (sdy/+) and homozygous (sdy/sdy) animals are normal in body weight, hair quality and density, number and length of whiskers, basic sensory abilities, neuromuscular strength, and sensorimotor reflexes (Hattori et al., 2008; Takao et al., 2008; Cox et al., 2009; Jentsch et al., 2009). In many other respects, they differ from littermate controls as described below.

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