Wild-type mice

Analysis of ESRB 7 mice showed fewer and smaller litters than wild type mice as well as abnormal vascular function and hypertension. The reduction in fertility was attributed to reduced ovarian efficiency. Mutant females had normal breast development and lactated normally. Older mutant males displayed signs of prostate and bladder hyperplasia. s -2-deficient mice furthermore display diverse regulatory defects in the function of brain, lung, and white blood cells. The results indicated that ESRB is essential for normal ovulation efficiency but is not essential for lactation, female or male sexual differentiation, or fertility. 

ELF, a (3-Spectrin, is a key component of TGF- 3 signaling that functions to recruit Smads to the receptor by controlling the subcellular localization of Smad 3 and Smad 4. Interestingly, ELF does not appear to interact with SARA or filamin, and in elf mutants, SARA and filamin distribution is the same as in wild-type mice. Thus, TGF- 3 signaling through R-Smad/ ELF interactions may work by way of a different mechanism than that of SARA and filamin. 

Studies on mixed gUal/neuronal cerebrocortical cultures from wild type mice and CXCR4-deficient mice show that HTV envelope proteins are able to cause neurotoxicity through CXCR4 or CCR5 by the activation of p38 and specific downstream effector... 

Compared to wild-type mice, in TRPVl gene-deleted (—/—) mice, complete Freund s adjuvant evokes significantly less oedema, hyperalgesia and arthritis score [149]. 

H3 knockout mouse H3 KO mouse is heavier than wild type mice [61] but see also [62]... 

Lyme arthritis C3H/HeJ, — Similar to wild-type mice 217... 

In order to explore the importance of the H3 receptor in sleep-wakefulness, Toyota et al. (2002) compared the wake-promoting effects of the H3 receptor antagonist thioperamide in wild-type and H3 receptor KO mice. In wild-type mice, subcutaneous administration of thioperamide (10 mg/kg) increased wakefulness with a concomitant decrease in NREM sleep during the first 2 h after administration at lights-on. REM sleep was unaffected. In contrast, thioperamide had no effect on sleep-wakefulness in H3 receptor KO mice (Toyota et al., 2002). 

The quantitation of spontaneous sleep-waking cycles in 5-HTiB receptor knockout mice has shown that REMS is increased whereas SWS is reduced during the light phase (Boutrel et al., 1999). On the other hand, systemic administration of CP-94,253 to wild-type mice tends to suppress REM, whereas the 5-HTiB antagonist GR 127935 induces the opposite effect. Thus, the limited available evidence indicates that 5-HTib receptor activation facilitates the occurrence of W and negatively influences REMS. 

A role for A2 Rs in sleep-wake regulation was also supported by studies in mice with constitutional knockout of A2ARs (Urade et al., 2003). Infusion into the lateral ventricle of CGS 21680 increased NREM and REM sleep in wild-type mice, but not in the knockouts. In contrast, the AiR agonist CPA did not affect sleep in either genotype, which indicated that AiRs could not compensate for the absence of A2aRs under these conditions. 

Studies in knockout mice indicate that the p2 nAChRs are necessary for nicotine self-administration, DA-dependent locomotor activation, and nicotine-associated enhancement of NAc DA release.40-51 53 Combined with studies showing that antagonism of the high-affinity nAChRs block self-administration,44-54 it would appear that p2 nAChRs are particularly critical for nicotine reinforcement. Unlike wild-type mice that self-administer both cocaine and nicotine, p2 nAChR-null mutant mice learn to self-administer cocaine normally, but stop bar pressing as though receiving saline when cocaine is switched to nicotine.40 Self-administration of VTA nicotine and associated DA release is rescued, however, in p2 nAChR knockout mice with lentiviral-mediated expression of P2 subunit DNA in the VTA.55 Whereas several configurations of the p2 nAChRs exist at the... 

A critical and IL-4-independent role for IL-13 has also been identified in host resistance to T. muris. Despite generating strong and equivalent type 2 responses to wild-type mice, mice deficient in IL-13 production failed to clear infection (Bancroft et al., 1998). Expulsion in BALB/c IL-4 KO mice was completely blocked following treatment with A25, confirming an important role for IL-13 in resistance to 1. muris (A.J. Bancroft et al., unpublished observations) (Table 17.1). In addition, IL-4 receptor KO mice (lacking IL-4 and IL-13 functions) are completely susceptible to T. muris (A.J. Bancroft, unpublished observations). 

Table 17.1. Mean worm burdens in IL-13 knockout (KO), IL-4 KO and wild-type mice at day 35 post-Trichuris muris infection.

IL-13 KO mice failed to clear infection despite mounting equivalent type 2 cytokine responses to wild-type mice. Further evidence of a role for IL-13 in expulsion is shown in studies utilizing BALB/c IL-4 KO mice. While control mice cleared infection, treatment with A25 (a soluble IL-13 receptor alpha 2-human IgG-Fc fusion protein) prevented worm expulsion. (Data adapted from Bancroft et al., 1998 A.J. Bancroft, unpublished.)... 

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