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PubMed1977

Hypoxanthine-guanine phosphoribosyltransferase activity in individual erythrocytes: autoradiographic studies in heterozygotes.

Heterozygotes for the Lesch-Nyhan syndrome have normal hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity in their erythrocyte lysates. However, HGPRT activity in lysates from heterozygotes for the partial HGPRT deficiency states is often between that seen in the affected hemizygote and the normal. An autoradiographic technique was developed which demonstrated the HGPRT activity in individual erythrocytes in vitro. This technique revealed that heterozygotes for the Lesch-Nyhan syndrome had erythrocytes that contained normal HGPRT activity but heterozygotes for the partial deficiency had two populations of erythrocytes, one with normal HGPRT activity and the other with the reduced HGPRT activity characteristic of the hemizygote. With these latter heterozygotes, the proportion of HGPRT-deficient erythrocytes agreed with that calculated on the basis of enzyme activity in erythrocyte lysates.

Autoradiography↗
PubMed2002

Fetal hemoglobin elevation in Hb Lepore heterozygotes and its correlation with beta globin cluster linked determinants.

We have analysed, at the hematological and molecular level, 51 Hb lepore heterozygotes and three compound heterozygotes for Hb Lepore and HbS (HbLep/HbS) in 26 unselected Portuguese families. The Lepore Boston variant was present in one family, in association with classical haplotype V. All of the other Lepore alleles present haplotype III in association with XmnI (+)5' of (G)gamma gene, in tight linkage disequilibrium to the major mutation found in the Portuguese population, the Lepore Baltimore variant ( delta(68Leu)-beta(84Thr)). The three compound heterozygotes are the first HbLep/HbS individuals reported in the literature, with the Lepore Baltimore mutation linked to haplotype III. In agreement with other studies, these Lepore Baltimore heterozygotes have higher HbF (1.4-14.1% of total hemoglobin) than published cases of Lepore Boston (0.8-5.4%), which is associated with XmnI(-). Among the Lepore Baltimore heterozygotes, the (AT)xTy repeat region at -540 bp of the beta globin gene in trans to the Lepore chromosome, can account for much of the variability in HbF level. The allele (AT)7T7 is associated with lower HbF, and (AT)9T5 is associated with higher HbF. As we previously reported for beta thalassemic carriers, we observe in Lepore Baltimore carriers an effector in trans, linked to the (AT)xTy sequence, acting as an HPFH (Hereditary Persistence of Fetal Hemoglobin) determinant.

Adolescent↗
PubMed2002

Investigations of micro-organic brain damage (MOBD) in heterozygotes of metachromatic leukodystrophy.

Potential damage of central and peripheral nervous system expressed as micro-organic brain damage (MOBD) was investigated in 27 unrelated heterozygotes with metachromatic leukodystrophy (MLD). Arylsulfatase A (ARSA) was determined in peripheral blood leukocytes and sulfatide excretion was estimated in 24-hour urine collections. Genomic DNA was analyzed for the ARSA pseudodeficiency (PD) allele by a PCR method. Clinical investigations included examination of hyper-reflexia, Babinski reflex, Wechsler Adult Intelligence Scale, Benton test, evoked potentials, and nerve conduction velocity (NCV). In our study, a higher incidence of evident or possible micro-organic brain damage was observed in true MLD/PD and MLD heterozygotes (NO/MLD, where NO means the wild allele) than in controls. On the basis of the Benton test, MOBD was suggested or indicated in 67% of MLD heterozygotes, 50% of MLD/PD heterozygotes, and 26% of controls. In our small group of carriers with MLD and PD mutations, persons NO/MLD(PD) with one wild-type allele did not show MOBD and displayed higher ARSA/beta-galactosidase ratios, unlike true MLD/PD compound heterozygotes who carry MLD-causing mutation in one allele and the ARSA-PD polymorphism in the second. Theoretically, this is a shift from autosomal recessive to autosomal dominant-like inheritance, especially when one cannot exclude the influence of polymorphisms (like ARSA-PD) in the wild allele. Since all psychological tests were age-matched, it can be assumed that the MOBD observed in MLD carriers does not have a progressive character unlike in MLD patients. However, it should be mentioned that MOBD appears to have no overt clinical consequences.

Adult↗
PubMedDate not supplied

Dermatoglyphic indices of males with the fragile X syndrome and of the female heterozygotes.

Indices for males with the fragile X [fra(X)] syndrome and for the female heterozygotes have been established. The indices were based on the increased frequencies of whorls and radial loops on the third digits of affected males and heterozygous females, increased frequency of arches on the third digits of the affected males, and an excess of low ab ridge counts and abnormal palmar creases, particularly the Sydney crease, in both sexes. The indices were calculated using the logN odds ratio based on the frequencies of the above dermatoglyphics and palmar creases in 47 males with the syndrome compared to 497 male controls and 36 heterozygous females compared to 493 female controls. The indices had similar distributions in males and females. Seventy per cent of males with the syndrome and 67% of female heterozygotes had an index greater than or equal to +0.5. Thirty-one per cent of female heterozygotes who had both the dermatoglyphic index calculated and their chromosomes examined under appropriate conditions for the fra(X) site had an index less than +0.5 and had less than 2% fragile sites (most had none). However when the two tests were considered together, only 4/35 (11%) of the heterozygotes would not have been identified using the two criteria. The data suggest that the dermatoglyphic index is a helpful adjunct test with chromosome analysis for the identification of fra(X) heterozygotes.

Adult↗
PubMed1995

Androgen receptor binding studies on heterozygotes in a family with androgen insensitivity syndrome.

A large family with androgen insensitivity syndrome (AIS) has been investigated, in order to detect carrier individuals and to investigate their AR binding. We have previously reported that different affected members of this family have different AR gene deletions, and, testing normal female relatives of the affected individuals, we have identified three heterozygote females all of whom carry a deletion of exon E of the AR gene. Androgen binding capacity was measured in cultured genital skin fibroblasts from normal male and female controls, the affected, and the heterozygote individuals in this family. A significant difference was found between the binding ranges for normal male foreskin and suprapubic skin fibroblasts (P < 0.005), and the three individuals with AIS had very low androgen binding capacity in their genital skin fibroblasts (2.6, 5.0, and 3.4 fmol 3HR1881/mg protein) compared to the normal range. The heterozygote females all had binding within the normal female suprapubic skin fibroblast range (12.5, 6.1, and 6.4 fmol 3HR1881/mg protein, respectively, for the three heterozygotes). Thus, we conclude that the absence of one functional AR gene in heterozygote females has not effect on AR binding capacity in cultured genital skin fibroblasts. In addition, bone mineral density was measured in the affected aunt and found to be significantly lowered at the lumbar spine (Z = -2.81) and hip (Z = -1.54); however, the role of the AR in determination of bone mineral density remains to be elucidated.

Adult↗
PubMed1993

Neuropathological study on cerebellum of macular mutant mouse heterozygote.

The hemizygote of the macular mutant mouse is clinically, biochemically and neuropathologically similar to a patient with Menkes kinky hair disease. The heterozygote of this mutant mouse was biochemically and neuropathologically examined. The copper content in the brain decreased in comparison with that in the normal littermate, although it was more than that in the hemizygote. In the Golgi study, abnormal Purkinje cells with somal sprouts, thick stem dendrites and dendritic focal swellings, which were seen in the hemizygote, were not observed in the heterozygote. Ultrastructurally, abnormal mitochondria were seen in the Purkinje cells in the anterior and middle cerebellar lobe of the heterozygote. Histochemically, cytochrome c oxidase activity decreased, especially at the anterior lobe in the cerebellar cortex of the heterozygote. This activity, as indicated by staining intensity, was in between that in the normal littermate and that in the hemizygote. The heterozygote did not show a mosaic pattern in the distribution of these neuropathological changes, although this mutant mouse shows x-linked recessive inheritance. Thus, our results lead to the conclusion that the neuropathological changes observed in this mutant mouse do not result directly from an abnormal gene in the Purkinje cell, but from the secondary effects of subsequent to presumptive copper deficiency.

Animals↗
PubMed1979

Heterozygote manifestation in recessive generalized myotonia.

The frequency of heterozygotes of recessive generalized myotonia may be estimated at about 1/108 in the German Federal Republic. Some heterozygotes can be identified by an EMG. However, apart from this, apparently 2%--5% of heterozygotes may show minor subclinical manifestations. Sporadic cases of myotonia with late onset and a history of preceding, extremely prolonged physical stress, undernourishment, and/or prolonged cold exposure may be due to heterozygote manifestations of this otherwise recessive gene. Late onset and sporadic appearance also are features in patients with myotonia associated with hypothyroidism. One male patient displayed myotonia after a protracted diabetic coma. In cases reported in the literature where myotonia developed in association with either propranolol (beta-adrenergic blocking agent) or fenoterolhydrobromide (stimulator of beta receptors) heterozygote manifestation of recessive generalized myotonia is suggested.

Adolescent↗
PubMed1986

Male pachytene pairing in single and double translocation heterozygotes and spermatogenic impairment in the mouse.

In order to clarify the relationship between meiotic pairing and progress of spermatogenesis, an analysis of male meiotic pairing was carried out in four reciprocal translocation heterozygotes and two double heterozygotes for two semi-identical reciprocal translocations. The reciprocal translocations were chosen to range from fertility (T70H/+) through almost complete sterility (T31H/+) to complete sterility (T32H/+, T42/H+). If meiotic pairing in the translocation multivalent was incomplete, it concerned terminal or probably more often proximal chromosome segments (Chain IV). If both segments failed to pair the multivalent symbol is Chain III + I. Complete pairing is symbolized by Ring IV. To contrast and complement observations of this type, the double heterozygotes were introduced. Males of this type in theory possess two heteromorphic bivalents with a central area of incomplete meiotic pairing (loop formation). Of the T70H/T1Wa double heterozygotes, 36% of the males are capable of inducing at least one decidual reaction in two females whereas for T26H/T2Wa, 79% of the males can do so. For the reciprocal translocations, it was found that proximity of the multivalent to the sex bivalent during pachytene increased in the order Ring IV, Chain IV, Chain III + I. The degree of spermatogenic impairment as measured from cell counts in histological sections and tubular whole mounts, is positively related to the frequency of proximity between the sex chromosomes and the translocation multivalent and thus to lack of meiotic pairing within the multivalent. The meiotic pairing analysis of the double heterozygotes yielded the following findings. For the long heteromorphic bivalents a true loop was never seen in T70H/T1Wa and only rarely observed in T26H/T2Wa. Small marker bivalents of both types were usually recognizable by the following criteria: pairing confined to distal or proximal segments, both distal and proximal segments pairing and loop formation and pairing covering the entire length of both "homologues" but the longer one often with a "thickened" lateral element. The same positive correlation between the absence of pairing (proximal, distal or central) and the proximity of the small marker bivalent synaptonemal complex to the sex bivalent has been found as for unpaired segments within reciprocal translocation multivalents. One unexpected finding was the occurrence of diploid spermatids and spermatozoa especially in T32H/+ males (70-91%) but also in T31H/+ (3-39%).

Animals↗
PubMed1981

Alpha-thalassemia and the production of different alpha chain variants in heterozygotes.

The production of five alpha chain variants (Hb G-Georgia, Hb St. Luke's, Hb Lloyd, Hb Montgomery, and Hb G-Philadelphia) in heterozygotes was evaluated through hematological observations, hemoglobin quantification, and biosynthetic studies. All heterozygotes for Hb St. Luke's and Hb Lloyd and most heterozygotes with Hb G-Georgia and Hb Montgomery had normal hematology and average sigma alpha/beta values of about 1.1. They were assigned a normal genotype (alpha alpha G/alpha alpha), although the proportions of Hb St. Luke's and Hb G-Georgia were low (10 to 13%) and those of Hb Lloyd and Hb Montgomery twice as high (20%). Data from short-term incubations confirmed this genotype for some of these heterozygotes. Isolated Hb St. Luke's and Hb G-Georgia gave low alpha G/beta values (0.2 and 0.3) indicating that these Hb variants were defective at the level of Hb assembly. Isolated Hb Montgomery and Hb G-Philadelphia, however, gave higher alpha G/beta values of 0.6 and 0.8, respectively. A second type of variability existed among Hb G-Georgia (20 vs. 13%), Hb Montgomery (28 vs. 20%), and Hb G-Philadelphia (47 vs. 34%) heterozygotes, in whom the levels of Hb G differed. The occurrence of higher levels of these three alpha chain heterozygosities was associated with hematological or biosynthetic evidence of a mild or moderate alpha chain deficiency due to an alpha-thalassemia-2 heterozygosity (alpha alpha G/alpha O alpha or alpha O alpha G/alpha alpha) or a homozygosity (alpha O alpha G/alpha O alpha), respectively.

Genetic Variation↗
PubMed1994

Severity of mutation in the phenylalanine hydroxylase gene influences phenylalanine metabolism in phenylketonuria and hyperphenylalaninaemia heterozygotes.

We examined whether the degree of residual activity from the mutant phenylalanine hydroxylase (PAH) allele affected phenylalanine metabolism in heterozygotes for phenylketonuria (PKU) or non-PKU hyperphenylalaninaemia (HPA). Discriminant analysis was carried out to find the function of fasting plasma concentrations of phenylalanine (PHE) and tyrosine (TYR) that best separated carriers from non-carriers. This function (0.103TYR -0.214-PHECORR -4.499) was subsequently used as the dependent variable, with the in vitro activity of the expressed mutant PAH as the independent variable, in a regression analysis performed on heterozygotes for mutations that had been studied in a eukaryotic cell expression system. This analysis showed a significant correlation (r = 0.40, n = 140, p < 0.001), although there was a wide spread of values within each of the two major groups of carriers and a considerable overlap between the groups. We conclude that the severity of the mutation, as determined by in vitro expression analysis, in the mutant PAH gene is reflected in the biochemical phenotype of heterozygotes. This result emphasizes the relevance of the cell expression system used for establishing the relative severities of most mutations at the PAH locus. Differences in the activities from the carried mutant PAH allele on phenylalanine metabolism in heterozygotes are, however, small compared to the activity from the normal PAH allele and are easily obscured by other factors leading to inter- or intra-individual variation in phenylalanine metabolism. Fasting plasma concentrations of phenylalanine and tyrosine thus can not be used to predict the severity of the carried PAH mutation in individual PKU or HPA heterozygotes.

Adult↗
PubMed1990

Macromolecular structure of axon membrane and action potential conduction in myelin deficient and myelin deficient heterozygote rat optic nerves.

The macromolecular structure of the axon membrane in optic nerves from 25-day-old male littermate control and myelin deficient (md) rats and 16-month-old md heterozygotic rats was examined with quantitative freeze-fracture electron microscopy. The axon membrane of control optic nerves displayed an asymmetrical partitioning of intramembranous particles (IMPs); P-fracture faces of myelinated internodal axon membrane were more particulate than those of pre-myelinated axons (approximately 1600 v 1100 microns-2, respectively), while relatively few IMPs (approximately 150 microns-2) were present on external faces (E-faces) of internodal or pre-myelinated axon membrane. Amyelinated axons of md optic nerves also exhibited an asymmetrical partitioning of IMPs; protoplasmic membrane face (P-face) IMP densities, taken as a group, exhibited a wide range (approximately 600-2300 microns-2) and, in most regions, E-faces displayed a relatively low IMP density (approximately 175 microns-2). Axons of greater than 0.4 microns diameter exhibited significantly greater mean P-face IMP density than axons less than 0.4 microns diameter. Aggregations of E-face IMPs (approximately 350 microns-2) were occasionally observed along amyelinated axon membrane from md optic nerves. Optic nerves from md heterozygote rats exhibit myelin mosaicism, permitting examination of myelinated and amyelinated axon membrane along the same tract. The axon membrane exhibits different ultrastructure in these two domains. Myelinated internodal axon membrane from md heterozygote optic nerves exhibits similar P- and E-face IMP densities to those of control internodal axolemma (approximately 1800 and 140 microns-2, respectively). Amyelinated axons in the heterozygote exhibit a membrane structure similar to amyelinated axons in md optic nerve. P-face IMP density of large diameter (greater than 0.4 microns) amyelinated axons from md heterozygote optic nerves is significantly greater than that of small calibre (less than 0.4 microns) axons. In most regions, amyelinated axon membrane exhibits a relatively low E-face IMP density (approximately 200 microns-2); however, focal aggregations (approximately 400 microns-2) of E-face particles are present. Electrophysiological recordings demonstrate that amyelinated axons in md optic nerves support the conduction of action potentials. Compound action potentials in md optic nerves exhibit a monophasic configuration, even at 20-days postnatal, similar to that of pre-myelinated optic nerve of 7-day-old normal rats. Moreover, conduction velocities in the amyelinated 20-day-old md optic nerve are similar to those displayed by pre-myelinated axons from 7-day-old optic nerves.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1989

Spontaneous CHO APRT heterozygotes reflect high-frequency, allele-specific deletion of the chromosome Z4 APRT gene.

In Chinese hamster ovary (CHO) cells, heterozygotes for the adenine phosphoribosyltransferase (APRT) locus arise spontaneously at high frequencies. Paradoxically, such heterozygotes yield APRT mutants only at much lower spontaneous rates, suggesting that the high-frequency event may occur at only one of the two APRT genes. In an attempt to understand the genetic basis for the apparent refractivity of one of the APRT alleles to the high-frequency genetic event and to determine whether differences in the genomic environments of the two CHO APRT alleles specifically render one gene more susceptible to high-frequency spontaneous deletion or inactivation, we have mapped the wild-type APRT allele in 16 independently derived spontaneous APRT heterozygotes. In 15 of these 16 heterozygotes, the functional, wild-type APRT gene was found to reside on the Z7 chromosome, indicating that the high-frequency event is indeed highly specific for the Z4 APRT allele. All but one of these heterozygotes were hemizygous for the APRT locus, suggesting that the high-frequency event generally involves deletion rather than spontaneous inactivation or mutation of the Z4 APRT allele.

Adenine Phosphoribosyltransferase↗
PubMed1985

Familial hypocalciuric hypercalcemia. Mild expression of the gene in heterozygotes and severe expression in homozygotes.

Autosomal dominant familial hypocalciuric hypercalcemia was found in a kindred with neonatal severe primary hyperparathyroidism, previously judged to be an autosomal recessive trait. Mild hypercalcemia was documented in eight members representing three generations. Mild hypercalcemia was documented at an age as early as one week. In seven adults presumed to be heterozygotes, urinary calcium levels were in the same range as for familial hypocalciuric hypercalcemia. An additional adult member (who previously underwent parathyroidectomy for neonatal severe primary hyperparathyroidism) showed an abnormality in renal clearance of calcium and sodium characteristic of combined familial hypocalciuric hypercalcemia and surgical hypoparathyroidism. Parathyroidectomy in three hypercalcemic members did not cause normocalcemia. Unlike other kindreds with familial hypocalciuric hypercalcemia in whom hypercalcemia is consistent over time and moderate in heterozygotes, this kindred was characterized by heterozygotes showing hypercalcemia that was intermittent and mild. The consanguineous parents of the two previously described severely affected neonates were judged to be heterozygotes for familial hypocalciuric hypercalcemia. In conclusion, (1) a gene presenting as familial hypocalciuric hypercalcemia can be expressed as hypercalcemia that is intermittent and very mild in heterozygotes; (2) such a gene can cause neonatal severe primary hyperparathyroidism in homozygotes.

Adolescent↗
PubMed2005

Heterozygote advantage and the maintenance of polymorphism for multilocus traits.

Explaining how polymorphism is maintained in the face of selection remains a puzzle since selection tends to erode genetic variation. Provided an infinitely large unsubdivided population and no frequency-dependance of selective values, heterozygote advantage is the text book explanation for the maintenance of polymorphism when selection acts at a diallelic locus. Here, we investigate whether this remains true when selection acts at multiple diallelic loci. We use five different definitions of heterozygote advantage that largely cover this concept for multiple loci. Using extensive numerical simulations, we found no clear associations between the presence of any of the five definitions of heterozygote advantage and the maintenance of polymorphism at all loci. The strength of the association decreases as the number of loci increases or as recombination decreases. We conclude that heterozygote advantage cannot be a general mechanism for the maintenance of genetic polymorphism at multiple loci. These findings suggest that a correlation between the number of heterozygote loci and fitness is not warranted on theoretical ground.

Alleles↗
PubMed1995

Recombination in single and double heterozygotes for two partially overlapping inversions in chromosome 1 of the house mouse.

Recombination frequency, chiasmata and chromatid interference were studied by means of analysis of meiotic configurations in diakinesis and metaphase II in single and double heterozygotes for the partially overlapping inversions In(1)1Rk and In(1)12Rk in chromosome 1 of the house mouse. Recombination frequency in the inverted regions was decreased in single heterozygotes and increased in the double heterozygotes as compared to normal homozygotes. Chiasmata in the inverted regions in the double heterozygotes did not interfere with each other. A significant excess of 4-chromatid double exchanges in the inverted regions was detected in the double heterozygotes.

Animals↗
PubMed1991

Chylomicron-remnant clearance in homozygote and heterozygote Watanabe-heritable-hyperlipidaemic rabbits is defective. Lack of evidence for an independent chylomicron-remnant receptor.

Lymph chylomicrons radiolabelled in triacylglycerol and cholesteryl ester were injected into control and Watanabe heritable-hyperlipidaemic (WHHL) rabbits. Clearance of chylomicrons was slower in heterozygote and homozygote WHHL rabbits. Slower remnant clearance in WHHL rabbits was confirmed by monitoring the clearance from plasma of preformed chylomicron remnants. Use of chylomicron-like lipid emulsions injected into control and WHHL rabbits also confirmed the defect in remnant clearance in heterozygote WHHL and homozygote WHHL groups. Clearance from plasma of emulsion triolein was delayed in both WHHL groups compared with controls, owing to slower remnant clearance. The clearance from plasma of radioiodinated rabbit low-density lipoproteins (LDL) in heterozygote WHHL rabbits was the same as control rabbits. Defective chylomicron-remnant removal but normal LDL clearance in the heterozygote WHHL corresponded to elevated concentrations of plasma triacylglycerol and normal concentrations of plasma cholesterol. Receptor versus non-receptor clearances of chylomicron remnants were studied by comparing the clearance of emulsions with and without unesterified cholesterol respectively. Unlike control rabbits, there were no significant differences in the clearances of the two emulsion types in either the homozygote or heterozygote WHHL rabbits, indicating that the apolipoprotein-B100/E receptor is the primary route for clearance of chylomicron remnants from plasma.

Animals↗
PubMed1999

Molecular, haematological and clinical studies of the -101 C --> T substitution of the beta-globin gene promoter in 25 beta-thalassaemia intermedia patients and 45 heterozygotes.

We report the clinical, haematological, biosynthetic and molecular data of 25 double heterozygote beta-thalassaemia intermedia patients and 45 beta-thalassaemia heterozygotes with the C --> T substitution at nucleotide position -101 from the Cap site, in the distal CACCC box of the beta-globin gene promoter. This mutation is considered the most common amongst the silent beta-thalassaemia mutations in Mediterranean populations. Of the 25 compound heterozygotes for the beta -101 C --> T and common severe beta-thalassaemia mutations, all but one had mild thalassaemia intermedia preserving haemoglobin levels around 9.5 g/dl and haemoglobin F levels < 25%. The only transfused patient was characterized to have an additional alpha-globin gene. Strict assessment of haematological and biosynthetic findings in the heterozygotes for the beta -101 C --> T mutation (excluding six cases with an alpha-globin gene defect) demonstrated that less than half of them had completely normal (silent) haematology; the remainder had either high haemoglobin A2 values (in the range of 3.7-5.1%) and/or low red cells indices and/or raised haemoglobin F values. The alpha/non-alpha-globin chain synthesis ratios were generally raised, with mean 1.44 (1.07-2.10). Amongst the parents of the compound heterozygotes, who were not selected for molecular analysis following haematological screening, half of the cases were completely silent. Interaction with severe beta-thalassaemia mutations always resulted in the clinical phenotype of mild non-transfusion-dependent thalassaemia intermedia.

Adolescent↗
PubMed1994

Fate of jimpy-type oligodendrocytes in jimpy heterozygote.

In the jimpy mutant mouse, as well as in many other animals with mutations in the myelin proteolipid protein (PLP) gene, oligodendrocytes degenerate before their maturation. To analyze whether this degeneration is caused by the loss of function of PLP gene products related to oligodendrocyte maturation/survival acting extrinsically, expression of the PLP gene was investigated in the jimpy heterozygote, in which one-half of the cells are jimpy type and the other half are wild type due to random X-chromosome inactivation. We first showed that jimpy PLP gene expression is normally regulated at the early stages of development in brains of jimpy hemizygotes and heterozygotes, at least to day 2 after birth. However, the great increase in the level of PLP gene transcripts observed in wild-type mouse brain is suppressed in jimpy mouse brain. This increase was also suppressed in the jimpy heterozygote, and by 2 months after birth, very few jimpy-type PLP gene transcripts were detected in heterozygotes. These results indicate that jimpy-type oligodendrocytes cannot survive or are still in the immature stage in the brain of jimpy heterozygotes. Thus, degeneration of jimpy oligodendrocytes is not caused merely by the lack of trophic factors.

Animals↗