span (Devlin et al., 1995a,b), and larval developmental rate (Devlin et al., 1995b).

Gene insertion and removal also can have effects on behavior—sometimes subtle. For example, growth hormone constructs in fish have been found to affect swimming ability (Farrell et al., 1997), feeding rates (Abrahams and Sutterlin, 1999; Devlin et al., 1999), and risk-avoidance behavior (Abrahams and Sutterlin, 1999). Some types of knockout mice also have been found to exhibit behavioral problems, such as increased aggressiveness and impaired maternal and spatial behaviors (Nelson, 1997) that are not immediately apparent, but that significantly could affect housing and care requirements.

Sometimes adverse effects are seen only when animals are challenged in some way. The abnormal stress response of the Beltsville pigs, when restrained, is an obvious example. In addition, some problems might not become evident until later in development. Mice transgenic for an immune system regulatory factor, interleukin 4, develop osteoporosis, but not until about two months of age (Lewis et al., 1993). This emphasizes the importance of monitoring the welfare of founder transgenic animals, and sometimes successive generations, throughout their lifetime using multiple criteria, including behavioral abnormality, health, and physiologic normality (Van Reenen et al., 2001). There has been only a limited number of studies of the welfare of transgenic farm animals to date, and detailed behavioral studies are particularly lacking.

NUCLEAR TRANSFER

Somatic cell nuclear transfer (NT) is a relatively new process (Chapter 1), and currently is very inefficient. High prenatal mortality and developmental abnormality, LOS, perinatal mortality, and abnormal placentation commonly are reported in cloned cattle and sheep (e.g., Wilson et al., 1995; Garry et al., 1996; Wells et al., 1997; Kato et al., 1998; Hill et al., 1999; 2000; De Sousa et al., 2001). Most mortality in cloned offspring appears to occur within the first few days after birth, although later mortality also is seen. Health and welfare problems reported in the immediate postnatal period include respiratory distress, lethargy, lack of a suckling reflex, cardiomyopathy, pulmonary hypertension, hydroallantois, hypoglycemia, hyperinsulinemia, urogenital tract abnormalities, pneumonia, and metabolic problems. However, such problems are not seen universally in cloned animals; many apparently healthy adult cattle, sheep, and goats have been cloned from adult, fetal, and embryonic cells (Lanza et al., 2001; Cibelli et al., 2002). For example, Wells et al. (1999) succeeded in producing 10 healthy calves from 100 transferred NT blastocysts; the calves were not exceptionally large, all had a strong suckling reflex, and only one required veterinary intervention. Lanza et al. (2001) report that the 24 dairy cows surviving from an original group of 30 cloned cattle are in normal physical



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