Biomedical subjects

Estelle Durand

Publications and source records attributed to Estelle Durand.

4 recordsLinked to original sources

PubMed2005

Sleep-disordered breathing in newborn mice heterozygous for the transcription factor Phox2b.

RATIONALE: Central congenital hypoventilation syndrome (CCHS) is a rare autosomal dominant syndrome present from birth, and characterized by depressed ventilation during sleep. Heterozygous mutations of the homeobox gene Phox2b were recently found in a very high proportion of patients. OBJECTIVES: To determine whether newborn mice with heterozygous targeted deletion of the transcription factor Phox2b would display sleep-disordered breathing. METHODS: We measured breathing pattern using whole-body plethysmography in wild-type and mutant 5-day-old mice, and we classified sleep-wake states using nuchal EMG and behavioral scores. RESULTS: We found that sleep apnea total time was approximately six times longer (8.9 +/- 12 vs. 1.5 +/- 2.2 seconds, p < 0.0015), and ventilation during active sleep was 21% lower (18.4 +/- 5.1 vs. 23.3 +/- 5.5 ml/g/second, p < 0.006) in mutant than in wild-type pups. During wakefulness, apnea time and ventilation were not significantly different between mutant and wild-type pups. Mutant and wild-type pups showed highly similar sleep-wake states. CONCLUSION: Although their respiratory phenotype was much less severe than CCHS, the Phox2b(+/-) mutant mice showed sleep-disordered breathing, which partially modeled the key feature of CCHS.

Animals↗

PubMed2005

Olfactory classical conditioning in newborn mice.

Determining the behavioural phenotype of genetically altered mice is a valuable approach for elucidating the function of genes and their role in cognitive disorders. Methods for phenotyping newborn mice are scarce and generally confined to sensorimotor reflexes. Here, we describe a simple method for assessing associative abilities in newborn mice. We used a two-odour-choice classical conditioning paradigm in mice from the day of birth (post-natal age 0, P0) to P6. Acquisition required 20 trials: 10 trials during which the pups were placed over the conditioned stimulus (CS+) odour (lemon or peppermint) for 30s and simultaneously stroked gently with a paintbrush and 10 trials during which the pups were placed over the other odour (CS-) for 30s, without stroking. Then, the pups were subjected to five odour-preference trials to test for conditioning. This sequence of five trials was repeated after 5 and 24h to assess retention of the conditioned odour preference. During the immediate post-acquisition sequence, the pups spent significantly more time over the CS+ than over the CS- (p<0.0001). No extinction of the conditioned preference was observed during this test. No preference was observed after 5 or 24h, indicating that the conditioned response was promptly lost. Conditioning was effective as soon as P0-P1. Thus, conditioning may emerge in newborn mice sooner than previously reported. This paradigm is well suited to phenotyping of large samples of genetically altered mice and may shed light on the role for genes in paediatric cognitive impairments.

Age Factors↗

PubMed2004

A simple method for short-term controlled anesthesia in newborn mice.

In this study, we describe a simple and inexpensive method for inducing short-term anesthesia and rapid recovery in newborn mice. Litters of Swiss mice pups were randomly allocated to testing on postnatal days 2, 5, and 8. Anesthesia was induced by placing the pup in a syringe and adding a volume of isoflurane-saturated gas that produced an estimated level of 32% isoflurane. Exposure to isoflurane lasted 30 s. All the pups survived the anesthesia. At all study ages, this method abolished the nociceptive response to tail clamp without inducing mortality, thus showing effective anesthesia. Recovery from anesthesia was assessed immediately after isoflurane exposure, based on two nonnoxious behavioral tests: the defensive response to a drop of water (10 tests, 1 min apart) and 10 min later the righting reflex, i.e., the time to recovery of the prone position (five tests, 10 min apart). The water drop test scores increased during the recovery phase toward the control values in all age groups. Treatment and time had no significant effect on righting reflex scores. The initial volume in the syringe, the volume of added isoflurane-saturated gas, and the duration of exposure may be adjusted according to postnatal age and specific strains or species (e.g., rats). This method is well suited to behavioral or physiological phenotype studies in developing mice, in which noxious procedures must precede functional testing, making rapid recovery from anesthesia a key requirement.

Age Factors↗

PubMed2002

Ventilatory responses to hypercapnia and hypoxia in heterozygous c-ret newborn mice.

The c-ret proto-oncogene encodes a tyrosine-kinase receptor involved in survival and differentiation of neural crest cell lineages. Previous studies have shown that homozygous c-ret-/- mice die soon after birth and have impaired ventilatory responses to hypercapnia. Heterozygous c-ret +/- mice develop normally, but their respiratory phenotype has not been described in detail. We used whole-body flow plethysmography to compare baseline breathing and ventilatory and arousal responses to chemical stimuli in unrestrained heterozygous c-ret +/- newborn mice and their wild-type c-ret +/+ littermates at 10-12 h of postnatal age. The hyperpnoeic and arousal responses to hypoxia and hypercapnia were not significantly different in these two groups. However, the number and total duration of apnoeas and periodic breathing episodes were significantly higher in c-ret +/- than in c-ret +/+ pups during hypoxia and post-hypoxic normoxia. These results are further evidence that respiratory control at birth is heavily dependent on genes involved in the neural determination of neural crest cells.

Animals↗