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Biomedical subjects

E W Henry

Publications and source records attributed to E W Henry.

11 recordsLinked to original sources

Long lives for homozygous trembler mutant mice despite virtual absence of peripheral nerve myelin.

Nervous system functions are dependent on point-to-point communication of signals along neuronal axons, and axonal insulation by myelin is thought to speed such conduction. Loss of previously formed myelin or lack of myelin formation can have serious, even fatal, consequences. Mice homozygous for the trembler mutation make virtually no peripheral nervous system myelin, yet have long and functional lives. This result calls into question the view that peripheral nervous system myelin plays a vital role, at least in this species.

Animals

Sex-influenced CPIB-induction of peroxisomes in rat lens tissue.

Male and female rats were used for the CPIB-administered inducement of peroxisomes in lens tissue. CPIB treatment enhances superoxide dismutase activity in both male and female rat lens tissue. CPIB causes a significant increase in catalase activity in male and a relatively smaller increase in female rat lens tissue.

Animals

Nerve regeneration through biodegradable polyester tubes.

One approach to repair of transected nerves is to attempt extrinsic guidance of axons across the gaps. We inserted the proximal and distal stumps of severed mouse sciatic nerves into opposite ends of biodegradable polyester tubes. The nerves and ensheathing tubes were examined after postoperative survival times of as long as 2 years. Myelinated fiber number in each successfully regenerated nerve was measured and correlated with the tube's residual lumen size. In selected regenerated nerves axonal sizes and myelin sheath widths were sampled and compared with control values. Swelling and deformation of tube walls occurred in nearly all tubes. Successful regeneration was obtained through more than half of the implants, and was more probable in tubes with larger initial lumens. Myelinated fiber number in regenerated nerves ranged from 231 to 3561 (normally 3900 to 4200); larger values again were found in tubes with larger initial lumens. Mean axonal areas in regenerated nerves were roughly half of normal, though myelin sheaths became appropriately thick. We concluded that the more biodegradable a tube, the more likely it was to incur distortion and luminal narrowing. Tube composition per se seemed of importance mainly as it related to maintenance of adequate luminal size over the length of the degrading tubes; luminal adequacy, not tube composition, seemed paramount in determining the extent of nerve regeneration.

Animals

Sex-influenced CPIB-induction of peroxisomes in rat liver and kidney tissues.

Male and female rats were used for CPIB-administered inducement of peroxisomes in liver and kidney tissues. Male rats respond to CPIB with higher levels of peroxisomal proliferation than females. Superoxide dismutase activity does not appear to be influenced by CPIB in any of the tissues studied. Aminotriazole depressed catalase activity in both males and females.

Animals

Comparison of Trembler and Trembler-J mouse phenotypes: varying severity of peripheral hypomyelination.

Trembler (Tr) is an autosomal dominant mutation which produces hypomyelination and demyelination in the mouse peripheral nervous system. This paper compares the genetic, behavioral, and pathological aspects of trembler-J, (TrJ) to those of the original Tr mutation. We found that TrJ was tightly linked on chromosome 11 to vestigial tail, vt, as is Tr. Most TrJ/? animals were more mildly affected behaviorally and pathologically than Tr/? animals. Tr/? animals were rather uniformly affected. In contrast, with matings of mildly affected TrJ/? (putative TrJ/+) animals to each other, and not with matings of putative TrJ/+ X +/+, some offspring, putative homozygotes, TrJ/TrJ, were more severely affected behaviorally and had more extreme peripheral hypomyelination than any Tr/? animals. In spite of their differences, Tr/?, putative TrJ/+, and putative TrJ/TrJ animals shared a failure or marked delay of Schwann cells to progress from the stage of axonal ensheathment in a 1:1 relationship to myelination. We conclude that Tr and TrJ are probably allelic, and that despite their phenotypic differences, their actions are fundamentally similar. While Tr is a dominant, we believe that TrJ behaves as a semidominant, which in homozygotes, TrJ/TrJ, produces the most severe heritable peripheral myelin deficiency hitherto described.

Alleles

The murine mutation trembler-J: proof of semidominant expression by use of the linked vestigial tail marker.

Trembler-J, TrJ, is a peripheral hypomyelinating murine mutant. In intercrosses (TrJ/ + X TrJ/ +) there are severely affected (behaviorally and pathologically), mildly affected, and normal offspring, while backcrosses (TrJ/ + X + / +) produce only mildly affected and normal offspring. We used the closely linked marker vestigial tail, vt, to test whether severely affected offspring of intercrosses (TrJvt/ + + X TrJvt/ + +) were TrJ/TrJ. In 5/6 intercrosses all severely affected animals were short-tailed and vice versa, while all mildly affected animals had long tails and vice versa. It is highly probable that the severely affected, mildly affected, and normal classes of intercross offspring were of TrJ/TrJ, TrJ/+, and +/+ genotypes, respectively.

Animals

Peripheral nerve repair with bioresorbable prosthesis.

Using the transected sciatic nerve model in adult mice, regeneration of a large bundle of axons organized into the form of a nerve with myelinated and unmyelinated axons, Schwann cells, fibroblasts, collagen, blood vessels, and connective tissue sheaths has been achieved with bioresorbable microtubular guidance channels over gaps of 5 mm in nonimmobilized animals. After 4-6 wks postoperatively, the regenerated nerve cable contains on the order of 40% as many myelinated axons as were measured in the proximal nerve stumps. With the channels used so far in this model, regenerating axons pass into the distal stump in about 3-6 wks postoperatively. The guidance channels used consist of synthetic polyesters and/or polyester composites including glycolic and lactic acid polymers, and polyesters derived from Krebs Cycle dicarboxylic acids. Inflammatory response to these materials has been minimal. Biodegradation/resorption rates can be controlled so as to be compatible with axon growth rates.

Animals

The mouse mutation claw paw: forelimb deformity and delayed myelination throughout the peripheral nervous system.

We describe a murine autosomal recessive mutation claw paw (gene symbol clp), which in homozygous clp/clp mice produces striking abnormalities of limb posture within the first one or two postnatal days. Affected animals have delayed and abnormal myelination in the peripheral nervous system but not in the central nervous system, and also have persistently blocked myelination of small caliber axons that are myelinated in normal mice. Both abnormalities suggest that an important effect of the clp mutation is to impair the putative signaling mechanism by which an axon instructs a Schwann cell whether or not to myelinate it. The early onset of behavioral abnormalities in clp/clp mutant mice, as well as certain other features of the disorder, suggest that some effects of the clp gene are not accounted for by the pathological findings. The clp gene has been mapped to chromosome 7 near the Gpi-1 locus.

Animals