The expression of inherited hydrocephalus in H-Tx rats (original) (raw)
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Single and multiple congenic strains for hydrocephalus in the H-Tx rat
Mammalian Genome, 2005
The H-Tx rat has fetal-onset hydrocephalus with a complex mode of inheritance. Previously, quantitative trait locus mapping using a backcross with Fischer F344 rats demonstrated genetic loci significantly linked to hydrocephalus on Chromosomes 10, 11, and 17. Hydrocephalus was preferentially associated with heterozygous alleles on Chrs 10 and 11 and with homozygous alleles on Chr 17. This study aimed to determine the phenotypic contribution of each locus by constructing single and multiple congenic strains. Single congenic rats were constructed using Fischer F344 as the recipient strain and a marker-assisted protocol. The homozygous strains were maintained for eight generations and the brains examined for dilated ventricles indicative for hydrocephalus. No congenic rats had severe (overt) hydrocephalus. A few pups and a significant number of adults had mild disease. The incidence was significantly higher in the C10 and C17 congenic strains than in the nonhydrocephalic F344 strain. Breeding to F344 to make F.H-Tx C10 or C11 rats heterozygous for the hydrocephalus locus failed to produce progeny with severe disease. Both bicongenic and tricongenic rats of different genotype combinations were constructed by crossing congenic rats. None had severe disease but the frequency of mild hydrocephalus in adults was similar to congenic rats and significantly higher than in the F344 strain. Rats with severe hydrocephalus were recovered in low numbers when single congenic or bicongenic rats were crossed with the parental H-Tx strain. It is concluded that the genetic and epigenetic factors contributing to severe hydrocephalus in the H-Tx strain are more complex than originally anticipated.
Hydrocephalus in the H-Tx Rat: A Monogenic Disease?
Experimental Neurology, 2000
The H-Tx rat is a genetic model of hydrocephalus for which thereis a poor understanding of the mode of inheritance. Previous studies suggested a polygenicmode of inheritance but the breeding data to supportthis hypothesis have not been reported. In an attempt to clarify the hereditary mode we have analyzed the data from eight generations of H-Tx rats and four generations of cross-matings between H-Tx rats and Sprague-Dawley (SD) rats. In the H-Tx rat colony 113 of 129 random brother-sister matings (87.60%) produced hydrocephalic offspring, with males and females being equally affected. The overall incidence varied greatly with an average of 30. 35%. In matings with more than three litters, all mating pairs yielded hydrocephalic pups. In cross-matings both hydrocephalic and normal H-Tx rats were mated with normal SD rats. No hydrocephalus was observed in the first generation of 124 pups (F1). Subsequent brother-sister matings of F1 animals generated hydrocephalic pups in the F2 generation with a lower incidence (4.67% in hydrocephalic HTx/SD matings and 5.11% in normal HTx/SD matings, respectively) than in the H-Tx rat colony (30.35%). Back-cross-matings between F2 rats and normal H-Tx rats yielded an incidence of hydrocephalus higher than that of the cross-matings but lower than that of the H-Tx colony. These data strongly suggest that the H-Tx rat is a homozygous carrier of an autosomal recessive hydrocephalus gene with incomplete penetrance. Furthermore, the data clearly rule out sex-linked and polygenic modes of inheritance and provide further insight with respect to genetic inheritance of hydrocephalus.
The Frequency of Inherited Hydrocephalus Is Influenced by Intrauterine Factors in H-Tx Rats
Experimental Neurology, 2002
H-Tx rats have fetal-onset inherited hydrocephalus. Linkage analysis has determined the genetics is complex, with at least three loci associated with hydrocephalus. In addition, maternal and/or intrauterine factors influence the frequency of expression. The aim of this study was to characterize nongenetic (epigenetic) factors that affect hydrocephalus in this strain. Groups of primiparous and multiparous females were used to breed fetuses for examination in utero. Multiparous females were manipulated to have either gestation with lactation or, by removal of pups at birth, gestation without lactation. In addition, hydrocephalus expression in postnatal rats from the breeding colony was analyzed for primiparous and multiparous females. The latter were subdivided according to the interval between the litter examined and the previous litter. There was no particular uterine position or horn that favored hydrocephalus and hydrocephalic fetuses were the same weight as normal littermates. The frequency of hydrocephalus was 16-20% in primiparous females and twofold higher in multiparous females that were lactating during pregnancy. Removal of the suckling pups prevented this increase. The severity of hydrocephalus was measured on 1-mmthick fixed brain slices. Fetuses from lactating females had hydrocephalus that was significantly more severe than the nonlactating groups. However, all fetus groups had hydrocephalus that was very much less severe than the postnatal pups, suggesting that severity increases after birth. It is concluded that there is an epigenetic factor that increases the frequency of inherited hydrocephalus in fetuses if suckling pups are present during gestation. Future experiments will examine possible mechanisms for this genotype-environment interaction.
Characteristics of hydrocephalus expression in the LEW/Jms rat strain with inherited disease
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 2003
The expression and severity of hydrocephalus was characterized in LEW/Jms rats with inherited hydrocephalus. The frequency of overt disease (lethal) was 27.7%, but varied depending on breeding line. It increased to 31.5% when rats with mild disease were included. Most breeding pairs (48/51) produced hydrocephalic offspring with significantly more males than females affected. Some adult rats were also found to have mild (nonlethal) ventricular dilatation. When bred to Fisher F344 rats, 3% of the F(1) progeny had overt hydrocephalus, indicating that the trait is not recessive. Overt hydrocephalus was 9-20% in N(2) rats (F(1) rats x LEW/Jms). The frequency of hydrocephalus and the presence of an excess of hydrocephalic males, varied depending on the direction of the cross. Mild hydrocephalus in N(2) rats was 3.1%. It is concluded that the inheritance of hydrocephalus in LEW/Jms strain is probably not mendelian recessive but may be semidominant or involve more than one gene and has a ma...
Cerebrospinal fluid research, 2005
The LEW/Jms rat strain has inherited hydrocephalus, with more males affected than females and an overall expression rate of 28%. This study aimed to determine chromosomal positions for genetic loci causing the hydrocephalus. An F1 backcross was made to the parental LEW/Jms strain from a cross with non-hydrocephalic Fischer 344 rats. BC1 rats were generated for two specific crosses: the first with a male LEW/Jms rat as parent and grandparent, [(F x L) x L], designated B group, and the second with a female LEW/Jms rat as the parent and grandparent [L x (L x F)], designated C group. All hydrocephalic and a similar number of non-hydrocephalic rats from these two groups were genotyped with microsatellite markers and the data was analyzed separately for each sex by MAPMAKER. The frequency of hydrocephalus was not significantly different between the two groups (18.2 and 19.9 %), but there was a significant excess of males in the B group. The mean severity of hydrocephalus, measured as the ...
Spontaneous Congenital Hydrocephalus in Sprague Dawley Rat
2014
Hydrocephalus is a neurological disorder that results from the accumulation of excess cerebrospinal fluid in the ventricles of the brain culminating in an enlarged cranium. This sporadic disorder may occur as a congenital malformation in many mammalian species including inbred rodent colonies at an early juvenile stage of life. Under conventional husbandry practice of breeding, 5 pups showing some clinical signs of neurological dysfunction at the age of 20 days were examined thoroughly. Detailed macroscopic examination demonstrated dome shaped head, thinned and deformed parietal bone, open/closed suture depending upon the severity of ventricular dilatation. Microscopic examination revealed dilated lateral ventricles, compressed and attenuated cortical mantle, spongy appearance of the sub-ventricular zone, stretched ventricular ependyma, flattened ependymal cell lining and infiltration of mononuclear cells in the ventricular lining.
Hereditary hydrocephalus internus in a laboratory strain of golden hamsters ( Mesocricetus auratus)
animal, 2008
Golden hamsters of one common laboratory strain had a high incidence of hydrocephalus internus. When a severity score of hydrocephalus was used, a major autosomal recessive locus could be identified. However, when a binary score (hydrocephalus, no hydrocephalus) was used, no such major locus could be detected and results of test matings were not consistent with Mendelian inheritance. Golden hamsters with severe forms of hydrocephalus had a dorsally compressed and ventrally intact hippocampus. Implications for the behavior and well-being of affected hamsters are unknown but researchers using this strain should be aware of the likely presence of hydrocephalus.
Genetics of Hydrocephalus (HC)
East African Scholars Multidisciplinary Bulletin
Genetic hydrocephalus is a neurological condition in which the cerebrospinal fluid (CSF) flows with subsequent and it results in enlargement of the cerebral ventricular cavities. The common cause of the congenital hydrocephalus is the variation in the L1CAM gene, and there is the narrow passage between the third and fourth ventricles. It is suggesting that hydrocephalus is more complicated than the simple CSF , and are many factors which are associated with the genetics of hydrocephalus, the major two factors are the i) telomeres proximity ii) and the more content of Adenine and Thymine [A, T] in the human CH as compared to the other nervous disorders. It is also suggesting that genetics of hydrocephalus is a crucial birth defect, and its genetics is still not completely understood, so it is the most important clinical feature. There are about 43 mutant loci associated with the animals and human hydrocephalus. Among them 9 are associated with animal models and 1 with the human. The ...
Hemorrhagic hydrocephalus (hhy): a novel mutation on mouse chromosome 12
Developmental Brain Research, 2004
A novel mouse hemorrhagic hydrocephalus mutation (hhy) inherited in an autosomal recessive manner on chromosome 12 has been found at the Osaka Prefecture University. The hhy homozygous mutant had dilated lateral ventricles and a communicating aqueduct, with no histological abnormalities either in the subarachnoid space or in the choroid plexus. Multiple hemorrhages in the meninges and throughout the brain parenchyma of the mutant were relevant to advanced stages of hydrocephalus. Subcortical heterotopia was detected unexceptionally in the mutants. Thus, the hhy mutation is characterized by three different abnormalities, i.e. hydrocephalus, intracranial hemorrhage and subcortical heterotopia.