Single Autosomal Recessive Gene Research Articles

New mutation causing jaundice in mice.

A new mutant causing jaundice in mice is reported. Allelism tests indicate that it is not allelic with known hemolytic anemia mutants in mice [hemolytic anemia (sphha), jaundiced (ja), normoblastic anemia (nb), and spherocytosis (sph and sph2Be)]. The jaundiced condition appears in young mice at about 24 hours postpartum and is due to a major increase in unconjugated bilirubin in serum compared to normal controls. Adult mutant mice are not jaundiced and bilirubin levels do not differ from normal mice. Adult male mutants have reduced testes size and no viable sperm. Female mutants are fertile but overall maternal performance is reduced as indicated by increased mortality and reduced growth rate of pups. Genetic tests indicate that a single autosomal recessive gene is responsible for the condition. We propose that the mutant be designated hyper-unconjugated bilirubinemia, with the gene symbol hub.

Distribution of slow myosin in dystrophic chicken muscle.

Avian muscular dystrophy is a disorder that preferentially affects the development of fast twitch muscles (215,218). Previous research using anatomical, histochemical, and biochemical methods have demonstrated clear dystrophic abnormalities in the posterior latisslmus dorsi (PLD) while the anterior latissimus dorsi (ALD), a slow tonic muscle, is unaffected by the disease (216,219). Most of this research has been performed on normal and dystrophic chickens of different genetic backgrounds. While avian muscular dystrophy is caused by a single autosomal recessive gene, the dystrophic gene causes relatively rapid fiber atrophy when placed on a New Hampshire background (217,220). These effects are most likely due to differences in the rate of muscle growth in the two breeds. Since inbred lines of normal and dystrophic chickens now exist that contain greater than 90% of their genes in common, these strains (normal line 03 and dystrophic line 433) were used for the current study to ensure that the differences observed between normal and dystrophic muscles were due to the disease.KeywordsMyosin Heavy ChainMedial GastrocnemiusDystrophic MuscleIntrafusal FiberSlow MyosinThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

A new mutant at the Dystrophia muscularis (dy) locus in the SM strain of mice.

Muscular dystrophy was found in the SM strain of mice. This defect was shown to be caused by a single autosomal recessive gene allelic with the genes at the dy locus. The dystrophic SM mice may provide a useful animal model for human muscular dystrophy, because SM strain has been selected for small body size and carries rare alleles at several loci.

Genetic control of natural resistance to Salmonella typhimurium in mice during the late phase of infection.

Previous studies have shown that C57L and DBA/2 mice are able to control the initial net growth of Salmonella typhimurium in splenic and hepatic tissues, but when infected i.p., they ultimately succumb to the typhoid-like disease caused by this Gram-negative bacterium. In this investigation, it was observed that the late-phase susceptibility of both the C57L and DBA/2 strains to murine typhoid was not only evident when mice were challenged i.p., but also when mice were challenged subcutaneously, i.v., and orally. Genetic analyses were then performed to characterize the gene or genes responsible for this susceptibility. The results of such experiments were consistent with the hypothesis that a single autosomal recessive gene is primarily responsible for the susceptibility. This gene was distinct from all other previously defined S. typhimurium response genes. The chromosomal location of the late-phase susceptibility gene could not be determined; no linkage was observed between expression of the late-phase susceptible phenotype and selected markers on chromosomes 1, 2, 4, 5, or 7.

Defective T cell response to presented antigen in autoimmune mice.

The effect of the single autosomal recessive gene lpr on antigen presentation was studied. MRL/Mp-lpr/lpr, C3H/HeJ-lpr/lpr, C57BL/6J-lpr/lpr, and their normal congenic partners were investigated. Mice bearing the lpr gene were unable to respond to TNP-KLH when presented by syngeneic antigen-presenting cells. The congenic normal partners gave a brisk response. Mixing experiments demonstrated that the defect resided with the lpr responding T cell and not with the lpr antigen-presenting cell. Antigen-presenting cells from lpr mice were capable of inducing T cell proliferation in normal congenic partners, whereas antigen-presenting cells from normal mice failed to stimulate lpr T cells. This defect was intrinsic to an Lyt-1+2- cell. Pharmacologic restoration was attempted by in vivo and in vitro administration of interleukin 2. However, cells from lpr mice remained unaffected. The relationship of these findings to autoimmunity is discussed.

Increased Susceptibility to Leishmania tropica Infection in Autoimmune MRL/MpJ-lpr Mice

Homozygous possession of the single autosomal recessive gene, lpr (lymphoproliferation) is associated with increased susceptibility to acute infection with Trypanosoma cruzi in four congenic strains of mice (Boyer et al., 1983, Parasit. Immunol. 5: 135-142). Animals bearing the lpr gene, which controls certain autoimmune and lymphoproliferative manifestations (Murphy and Roths, 1978. In Genetic Control of Immune Disease, N. R. Rose, P. E. Bigazzi, and N. L. Warner (eds.). Elsevier North Holland, Amsterdam, pp. 207-220), show increased parasitemia or mortality when compared to their congenic partners that lack the gene. In the study described here we sought to determine if possession of the lpr gene might also influence susceptibility to another protozoan parasite, Leishmania tropica. Our data indicate that female MRL/MpJ-lpr mice injected with L. tropica promastigotes are susceptible to the infection, whereas their congenic partners, MRL/MpJ-+, are resistant to an identical dose of parasites. Because the two strains are of the same haplotype (H2k) and differ only in possession of the lpr gene, our results suggest that this single, non-H2-associated gene can influence susceptibility to infection with L. tropica. Leishmania tropica (WR 309) amastigotes were aspirated by needle from the lesions of infected BALB/cJ mice and allowed to transform into promastigotes. Eight-wk-old female MRL/ MpJ-lpr and MRL/MpJ-+ mice (Jackson Laboratory) were infected via subcutaneous injection of 5 x 107 organisms into the left rear footpad. The right rear footpad was injected at the same time with phosphate-buffered saline and footpad measurements (mm) made weekly with a Pocotest micrometer. The measurements on the MRL strains and additional C57BL/6J and BALB/cJ animals were expressed as the ratio between right and left footpad thicknesses. As seen in Figure 1 the two congenic MRL strains responded differently to infection with L. tropica. The MRL/MpJ-lpr mice were unable to control the parasites and showed a slow progressive expansion of the lesion. This result, albeit less pronounced than that found in L. tropica-sensitive BALB/cJ (H2d) mice is similar to that reported in DBA/1 animals (H2q) (Howard et al., 1980, Parasit. Immunol. 2: 303-314). Surviving MRL/MpJ-lpr animals also had metastatic lesions. MRL/MpJ-+ mice showed a pattern of lesion development similar to that of C57BL/6J (H2b) animals. Data on the genetic factors that influence susceptibility to L. tropica infection indicate substantial differences between mouse strains (Cox, 1981, Nature 291: 111-112). These differences appear to be largely H2-independent, although a certain retarding influence of H2k on the later stages of lesion growth has been observed in animals with the susceptible BALB/c (H2d) background (Howard et al., 1980, op. cit.). The hypersusceptibility of BALB/c mice is determined

Shaker short-tail, a spontaneous neurological mutant in the mouse

A spontaneous mutation that occurred in the Inbred strain BALB/cCF In 1980 proved to be inherited as a single autosomal recessive gene with complete penetrance. Homozygous recessive animals have a short or blunt tall, an irregular pattern of foliation of the cerebellum, delayed development of the righting reflex, and a wide variety of other peculiar behaviors. The effects of this mutation strongly resemble those of the shaker-short (st) gene reported by Dunn in 1934 that is now extinct. The gene designation, sst, is proposed for the new shaker short-tall mutation.

Further evidence on the inheritance of halothane reaction in pigs.

One thousand six hundred forty-one Pietrain, 163 Minnesota No. 1 and 158 Pietrain X Minnesota No. 1 crosses and their reciprocals were tested for porcine stress syndrome susceptibility using halothane gas between September 1975 and July 1981. The frequency of reactors in the Pietrain breed was 93.9%. Matings of reactor males to reactor females within the Pietrain breed resulted in 632 reactor and 14 nonreactor offspring. A boar, judged to be nonpenetrant on the basis of the halothane reaction of his parents and littermates, was shown by progeny test to be homozygous for the halothane allele. These data indicate that halothane sensitivity is due to a single autosomal recessive gene with a penetrance of about 98% and a frequency of .98 in this Pietrain herd. No halothane reactors were found in the 163 Minnesota No. 1 pigs tested. Only one Pietrain X Minnesota No. 1 gilt reacted positively to halothane and later, the same gilt produced both positive and negative offspring, indicating that she was most likely heterozygous. Blood group typing of 107 crossbred pigs provided insufficient information to predict accurately the halothane reaction, although some associations were observed between the A and H loci and halothane sensitivity. The time taken by Pietrain pigs to react to halothane was measured and recorded. Analysis of these data showed that progeny of some sires had significantly faster reaction times than others and that reaction time had decreased over the years. These results as well as other data presented here indicate the existence of certain modifier genes that influence halothane reaction.

Genetics of the diplopodia-5 mutation in domestic fowl

The diplopodia-5 condition in fowl is caused by a single autosomal recessive lethal gene, dp-5, having complete penetrance and variable expressivity. Linkage tests with marker genes for naked neck, pea comb, rose comb, and dominant white were negative. A breeding test indicated that dp-5 and dp-3 are not allelic. Literature descriptions of dp-1, dp-2(extinct), and dp-4 (sex-linked) indicate that dp-5 differs from all of them. Diplopodia-5 embryos are tharacterized by extra digits on the preaxial side of the limbs, supernumerary metatarsal and metacarpal bones, shortened limbs and upper beak, reduced body weight and length, and inability to hatch.

Short Barb: A Feather Structure Mutation in Japanese Quail

A type of feather structure abnormality in Japanese quail resulting in shortened barbs on contour feathers was found to be controlled by a single autosomal recessive gene, sb (short barb). The mutation was first identified in a full-sib family from the University of British Columbia wild type line. Unlike other feather structure mutations in Japanese quail reported previously in literature, the short barb mutation is not associated with poor reproduction.

“Porcupine”: A Feather Structure Mutation in Japanese Quail

A type of feather structure abnormality in Japanese quail resulting from the failure of barbs to uncoil was found to be controlled by a single autosomal recessive gene, pc (porcupine). The mutation was first identified in two birds from a population homozygous for white plumage color. Porcupine quail have poor egg production, lower fertility, and higher embryonic and chick mortality compared to wildtype or heterozygotes.

Canine model of narcolepsy: Genetic and developmental determinants

Genetic and developmental factors were investigated in 101 cases of canine narcoleps-cataplexy syndrome. An experimental breeding program documented a probable autosomal recessive mode of inheritance in two dog breeds, Doberman pinschers and Labrador retrievers, and in crosses between those breeds. Age of onset of cataplexy and severity of symptoms were remarkably similar in 73 subjects with the genetically transmitted form of narcolepsy. Efforts to demonstrate genetic factors by breeding affected poodles and beagles were unsuccessful. Furthermore, a positive family history could not be documented in these animals or in narcoleptic dogs of 13 other breeds. Both age of onset and severity of symptoms were highly variable within this population. We suggest there may be multiple etiologies in canine narcolepsy syndrome: (i) inheritance via a single autosomal recessive gene, which appears to be identical in at least two unrelated dog breeds; (ii) nongenetic mechanisms which may include developmental or traumatic accidents. Preliminary findings of parallel neurochemical studies in narcoleptic dogs indicate distinct abnormalities in central neurotransmitter concentration and turnover. We theorize that these neurochemical abnormalities may result from inherited disorders of synthesis and/or metabolism which are present from birth or from nongenetic neurochemical abnormalities appearing later in life. The observation that symptom characteristics are identical in all affected dogs suggests that a common neurochemical disorder may underlie both genetic and nongenetic variations of the disease.

Deficient interleukin 2 activity in MRL/Mp and C57BL/6J mice bearing the lpr gene.

Spleen cells from MRL-lpr and B6-lpr mice have a marked defect in the ability to produce interleukin 2 (IL-2) in response to concanavalin A stimulation. This defect precedes the onset of clinical illness, increases with age, and eventually becomes virtually absolute. It is not due to cellular suppression of IL-2 production, nor does it reflect the presence of a soluble inhibitor of IL-2 activity. Failure to restore IL-2 production with macrophage-replacing factors, such as interleukin 1 and phorbol myristic acetate, suggests that IL-2 deficiency reflects a primary T cell defect rather than a macrophage defect. MRL-lpr and B6-lpr spleen cells also have an age-dependent reduction in IL-2 response that apparently results from a deficiency of cell surface receptors for IL-2. Congenic MRL-+/+ and B6-+/+ mice, which lack the lpr gene responsible for accelerated autoimmunity and lymphoproliferation, have normal IL-2 activity. These findings suggest that a defect in IL-2 activity may contribute to impaired immunoregulation in mice bearing the lpr gene. The absence of such a defect in MRL-+/+ and B6-+/+ mice further suggests that a single autosomal recessive gene is responsible for IL-2 deficiency.

Inheritance of the ability of strains of Sitophilus oryzae (L.) (Coleoptera: Curculionidae) to breed on split-pea (Pisum sativum)

AbstractSitophilus oryzae (L.) is a pest of stored grain, hut most strains tested so far fail to breed on yellow split-peas (Pisum sativum) and these can be used in admixture to protect other grains from infestation by the weevil. However, seven strains of S. oryzae have been found to breed on yellow split-peas, and the inheritance of this ability was investigated in two of these strains, one from Lesotho and the other from Trinidad. In each strain, the pattern of inheritance showed that the ability to breed on split-peas was controlled by a single autosomal recessive gene. It was not possible to distinguish whether the same genetic locus was involved in each strain. Control is either by two alleles at the same locus or by functionally similar alleles at different loci. There was some evidence that the genetic background of the two strains is different and that the Lesotho strain carries a sex-linked lethal gene. The existence of a heritable ability of some strains of s. oryzae to breed on split-peas suggests that the usefulness of admixture of split-peas with other grain may be limited

The mode of development of an inherited form of anencephaly in the house mouse.

Anencephaly in the xn strain of mouse is a condition determined by a single autosomal recessive gene. At birth, affected animals bear a cap of degenerate cerebral tissue devoid of bony covering. The early development of this malformation was studied in embryo mice from the stage of neural groove formation until after the neural tube has normally closed. The abnormal embryos could be recognized before the anterior neuropore had completely closed in normal litter mates. Detection of the cerebral malformation at this early stage of gestation suggests that the inherited murine anencephaly is due to primary failure of the neural tube to close.

Inheritance of delta 9-tetrahydrocannabinol seizure susceptibility in rabbits.

Delta 9-Tetrahydrocannabinol (THC), the major psychoactive ingredient of marijuana, causes nonfatal convulsions in rabbits of a closed colony of New Zealand White rabbits (Uaz: NZW). The convulsive phenotype appears to be associated with homozygous expression of a single autosomal recessive gene with full penetrance. We propose the symbol thc for the gene responsible for this condition. We also propose that this closed colony of New Zealand White rabbits at the University of Arizona, in which the thc gene is segragating, be designated Uaz:NZW-thc.

A new mutant in the mouse: peroneal muscular atrophy (author's transl)

An anomaly of the hind limb has been found in the process of inbreeding of the CF#1 strain. The affected mouse showed a club foot at birth and unusual gait by a dropped foot in the adult. The growth of the affected mouse was slightly delayed in comparison with normal littermates, but reproductive performance was almost normal in both sexes. Anatomical and pathological studies revealed the atrophy of the peroneal muscle group and absence of the common peroneal nerves. The genetical studies showed that this anomaly was mainly controlled by a single autosomal recessive gene. The penetrance and expressivity of the gene was complete in the original or related strains, but incomplete in the other genetic backgrounds. This major gene has been named peroneal muscular atrophy (gene symbol: pma).

An Autosomal Recessive Blind Mutant in the Chicken

A type of blindness due to lack of rods and cones in the retina was found to be controlled by a single autosomal recessive gene, rc. The mutation was first identified in the second generation decendents of a male carrying an ethyl methanesulfonate (EMS) induced chromosome translocation involving one arm of the Z sex chromosome and the long (q) arm of chromosome 3. A linkage test between the locus causing the blindness and the translocation break-point on chromosome 3 was not significant. There is no proof that the mutation was EMS induced.

First arch malformation: a new craniofacial mutant in the mouse.

The first arch malformation arising in a BALB/c strain of mice, has been shown to be inherited as a single autosomal recessive gene and is given the provisional gene symbol far. Affected newborns have extensive bony defects of the face and skull, including a cleft secondary palate, and die within 24 hours of birth. Most of the abnormalities occur in bones derived from the first branchial arch and most of the bony derivatives of the first arch are abnormal in the mutant.

Insulin dependent diabetes: A comparison of families with single and multiple affected siblings

Families (n = 14) with more than 1 sibling with insulin dependent diabetes were matched with families of similar size and age distribution containing only 1 affected child. The distribution of HLA haplotypes, age of onset of disease, and seasonal onset of disease were compared in the two groups. The data are not consistent with the hypothesis of a single autosomal recessive gene linked to the HLA region. The data do not permit a choice between other current hypotheses although they are compatible with the theory of 2 genes linked to the HLA region, acting additively, and requiring interaction either with environmental factors or other disease susceptibility genes. Diabetic children in the multiplex and simplex families did not differ in the month of onset of symptoms nor in the age at diagnosis although three multiplex pedigrees in which diabetes developed in all affected children before the age of 6 years were identified.