Apelin constitutes a novel endogenous peptide system suggested to be involved in a broad range of physiological functions, including cardiovascular function, heart development, control of fluid homeostasis, and obesity. Apelin is also a catalytic substrate for angiotensin-converting enzyme 2, the key severe acute respiratory syndrome receptor. The in vivo physiological role of Apelin is still elusive. Here we report the generation of Apelin gene-targeted mice. Apelin mutant mice are viable and fertile, appear healthy, and exhibit normal body weight, water and food intake, heart rates, and heart morphology. Intriguingly, aged Apelin knockout mice developed progressive impairment of cardiac contractility associated with systolic dysfunction in the absence of histological abnormalities. We also report that pressure overload induces upregulation of Apelin expression in the heart. Importantly, in pressure overload-induced heart failure, loss of Apelin did not significantly affect the hypertrophy response, but Apelin mutant mice developed progressive heart failure. Global gene expression arrays and hierarchical clustering of differentially expressed genes in hearts of banded Apelin(-/y) and Apelin(+/y) mice showed concerted upregulation of genes involved in extracellular matrix remodeling and muscle contraction. These genetic data show that the endogenous peptide Apelin is crucial to maintain cardiac contractility in pressure overload and aging.

Abstract. Microtubule-associated proteins such as MAP1B have long been suspected to play an important role in neuronal differentiation, but proof has been lacking. Previous MAP1B gene targeting studies yielded contradictory and inconclusive results and did not reveal MAP1B function. In contrast to two earlier efforts, we now describe generation of a complete MAP1B null allele. Mice heterozygous for this MAP1B deletion were not affected. Homozygous mutants were viable but displayed a striking developmental defect in the brain, the selective absence of the corpus callosum, and the concomitant formation of myelinated fiber bundles consisting of misguided cortical axons. In addition, peripheral nerves of MAP1B-deficient mice had a reduced number of large myelinated axons. The myelin sheaths of the remaining axons were of reduced thickness, resulting in a decrease of nerve conduction velocity in the adult sciatic nerve. On the other hand, the anticipated involvement of MAP1B in retinal development and ␥ -aminobutyric acid C receptor clustering was not substantiated. Our results demonstrate an essential role of MAP1B in development and function of the nervous system and resolve a previous controversy over its importance.

In the present study 125 cats with recurrent seizures were analysed. The main goal was to investigate the aetiology and compare primary epilepsy (PE) with secondary epilepsy (SE) regarding signalment, history, ictal pattern, clinical and neurological findings. Seizure aetiology was classified as PE in 47 (38%) and SE in 78 (62%) cats. SE was caused mainly by intracranial neoplasia (16), hippocampal necrosis (14), toxicosis (eight), and encephalitis (seven). A significant difference between PE and SE was found in: age, body weight, duration of seizure, occurrence of status epilepticus and neurological deficits. Status epilepticus, altered interictal neurological status and seizure onset over the age of 7 years indicated SE more frequently than PE. If the seizures occurred during resting conditions and rapid running occurred the aetiology was more likely to be PE than SE.

Seventeen cats were presented with acute onset of complex partial seizures with orofacial involvement (salivation, facial twitching, lip smacking, chewing, licking or swallowing), motor arrest (motionless starring) and behavioural changes. In 11 cats hippocampal necrosis (HN) was confirmed by histopathology. In a further six cats hippocampal changes were suggested by magnetic resonance imaging. The mean monitoring time of eight cats which were not euthanased in the acute phase of the disease, was 408 days (60-908): four cats are still alive. In all surviving cases, the owners reported a good quality of life. We conclude that an acute cluster of complex partial seizures with orofacial involvement are often associated with HN and that HN is not necessarily a fatal condition. Supportive and antiepileptic therapy can result in remission. The long-term outcome can be good to excellent; therefore, euthanasia should be avoided in the acute phase of the signs.

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