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L L Washburn

Publications and source records attributed to L L Washburn.

32 records · Page 2Linked to original sources
PubMed1983

Sex reversal in XY mice caused by dominant mutation on chromosome 17.

A Y-linked gene(s) is undoubtedly a prerequisite for testicular development in mammals. However, exceptional cases suggest that the mere presence of the Y chromosome or the Y-linked testis-determining gene does not totally control the fate of the bipotential gonad. For example, in the mouse, a major as yet unmapped autosomal locus is necessary for normal testicular development and at least one additional autosomal locus is implicated. We present here a third autosomal sex-determining locus. This dominantly inherited trait, tentatively named T-associated sex reversal (gene symbol Tas), is closely linked to or a part of the T/t complex on chromosome 17 of the mouse. Gonads of chromosomally XY individuals who inherit Tas on the C57BL/6J inbred strain background differentiate as ovaries or ovotestes.

Animals↗
PubMed1983

Inherited sex reversal in mice: identification of a new primary sex-determining gene.

We present evidence that the inbred mouse strain C57BL/6J (B6) differs from Mus domesticus (DOM) at a locus involved in gonad determination and development as well as at the testis-determining locus on the Y chromosome (Tdy). This newly identified gene is named testis-determining, autosomal-1 (tda-1). Although the inheritance of tda-1 suggests it is located on an autosome, its location on the X and Y chromosome in their pairing-recombination region is not excluded. When mice are homozygous for the C57BL/6J-derived tda-1 allele (tda-1B6) and carry the Y chromosome from M. domesticus, they develop as true hermaphrodites or, more rarely, as females. In contrast, when they are homozygous Tda-1DOM/Tda-1DOM or heterozygous Tda-1/DOMtda-1B6 and carry a B6-derived or M. domesticus-derived Y chromosome they develop as normal males. A simple genetic model is presented that integrates proposed steps in gonad determination and the results from genetic experiments reported here. In addition, arguments are presented for the existence of an ovary-determining gene.

Animals↗
PubMed1983

H-Y typing of karyotypically abnormal mice.

It has been proposed that the male-specific transplantation antigen H-Y is the trigger for testis formation (Ohno's hypothesis). We have tested this hypothesis by examining the H-Y status of a number of mice with abnormal or aberrant karyotypes relative to their gonad development. This analysis includes the discussion of published results of XX males carrying the Sxr mutation and XO females, and the presentation of unpublished data from XY females carrying the YPOS or YORB chromosome, XY females carrying Thp on chromosome 17, and a series of mice carrying X-Y recombination products derived from the Y* chromosome. The XX Sxr males have testes and are H-Y transplantation antigen positive; XO females have ovaries and are H-Y negative; mice with X-Y reciprocal recombinant chromosomes resulting from an abnormal Y chromosome show concordance between the presence of testes and the presence of the H-Y antigen. All of these findings are in accord with Ohno's hypothesis. In contrast are our findings that three types of C57BL/6J XY females are H-Y positive, two inheriting a Y chromosome from the mouse species Mus domesticus, either YPOS or YORB, and the other a mutation associated with Thp. Genetic analysis of the inheritance of this paradoxical phenotype indicates that normal testis differentiation involves the interaction of two or three genes, and is not simply a function of a Y-linked gene product. We conclude that H-Y is not the sole Y-linked testis determining gene.

Animals↗
PubMed1980

A cytogenetic investigation of inherited true hermaphroditism in BALB/cWt mice.

A predictably high incidence of true hermaphroditism (3%) among fetal BALB/cWt mice provided the opportunity for studying the cause of inherited hermaphroditism. G-banded liver metaphase chromosomes were analyzed from 20 fetal hermaphrodites and from 15 normal female and male littermate controls. All hermaphrodites and seven males were chromosomal mosaics, i.e. XO/XY or XO/XY/XYY. In each mosaic fetus there were more XO than XYY cells. From these findings we hypothesize that BALB/cWt hermaphrodites arise from non-disjunction and probable loss of the Y-chromosome during mitosis. Results from breeding experiments indicated that a defect in the BALB/cWt Y-chromosome per se accounts for its nondisjunction and loss. A significant relationship was found between the amount of ovarian tissue and the percentage of XO cells in mosaic fetuses. If all chromosomally mosaic (XO/XY and XO/XY/XYY) individuals are considered, ovarian tissue was formed if there was 24% or more XO cells in an individual. If only hermaphroditic individuals are considered, ovarian tissue was formed if there were 44% or more XO cells. Finally, we found that the distribution of ovarian and testicular tissue within an ovotestis of BALB/cWt hermaphrodites was not random: ovarian tissue was situated at both ends or only at the cranial end; in only one case was ovarian tissue situated in the center flanked by testicular tissue. We suggest that such nonrandom distribution of ovarian and testicular tissue argues against the hypothesis that the organization of testicular tissue is dependent only on the presence of H-Y antigen.

Animals↗
PubMed1979

Colinearity in the mouse genome: a study of chromosome 2.

The cytologic positions (determined by G-banding) of the breakpoints on mouse chromosome 2 of a series of ten reciprocal translocations were compared with their most probable genetic positions on the linkage map, as determined by studies on recombination with known chromosome 2 (= linkage group V) markers. The most probable proximaldistal orders of the genetic and cytologic breakpoints were found to be the same; i.e., the two sets of breakpoints were colinear. However, there was no close correspondence between these two measures of the distance apart of adjacent breakpoints, since some translocation breaks which were well separated in G-band positions seemed close together in terms of the linkage map, and vice versa. This helps to confirm LYON'S conclusion that in certain mouse chromosomes, including No. 2, the distribution of chiasmata is nonrandom.

Animals↗
PubMed1978

Assignment of genes to regions of mouse chromosomes.

A genetic mapping procedure, called the duplication-deficiency method, is described. This method permits the genetic location of a translocation to be determined within a linkage group without the use of recombination. By utilizing the duplication-deficiency method to define the genetic breakpoints for a series of translocations involving a given chromosome and integrating this information with their cytological breakpoints, obtained by Giemsa banding, a genetic map of the chromosomes is constructed whereby groups of loci are assigned to banded regions. Duplication-deficiency mapping and Giemsa banding analysis of the T(X;7)1Ct and T(7;19)145H translocations together with information from the c25H deletion have permitted mouse chromosome 7 to be divided into six and chromosome 19 into two definable genetic regions.

Animals↗
PubMed1975

Hormonal regulation of lobulo-alveolar growth, functional differentiation and regression of whole mouse mammary gland in organ culture.

The entire second thoracic mammary glands of 4-week-old BALB/c female mice primed with oestradiol plus progesterone were cultivate in organ culture medium containing the "growth-promoting" hormone combinations: insulin, prolactin, growth hormone, oestradiol, progesterone and aldosterone or insulin, prolactin and aldosterone. Full lobulo-alveolar development was induced after 5-6 days of incubation and could be maintained for 15-16 days in organ culture in medium containing either hormone combination. After the initial 5-6 days in the "growth-promoting" medium, subsequent cultivation of the glands in a medium with the "lactogenic hormones", insulin, prolactin plus cortisol, led to accumulation of "milk-like" secretory material in the ductal and alveolar lumina. Incubation of the lobulo-alveolar gland in medium with insulin alone for 7-9 days resulted in complete regression of the alveoli leaving only a ductal parenchyma. Incubation in insulin, prolactin, growth hormone or insulin plus the steriod hormones for 7-9 days led to considerable alveolar degeneration without a complete regression. The results indicate that both pituitary and steroid hormones are essential for development and maintenance of mammary alveoli; insulin can only sustain the basal ductal structure.

Aldosterone↗
PubMedDate not supplied

Inheritance of T-associated sex reversal in mice.

We previously identified a primary sex-determining locus, Tas, on mouse Chr 17 that causes ovarian tissue development in C57BL/6J Thp/+ and TOrl/+ individuals if the AKR/JY chromosome is present. We hypothesized that Tas is located within the region of Chr 17 deleted by Thp and TOrl and that C57BL/6J carries a diagnostic Tas allele, based on the observation that ovarian tissue develops in XY mice when Thp is on a C57BL/6J inbred strain background, whereas normal testicular development occurs when Thp is on a C3H/HeSnJ inbred strain background. To test this hypothesis, we mated (C57BL/6J x C3H/HeSnJ)F1 females to C57BL/6J Thp/+ hermaphrodites. As expected, half of the XY Thp/+ offspring developed ovarian and testicular tissue while half developed exclusively testicular tissue. Unexpectedly, the inheritance of selected Chr 17 molecular loci was independent of gonadal development, as half of the male and hermaphroditic offspring inherited C3H/HeSnJ-derived Chr 17 loci and half inherited C57BL/6J-derived Chr 17 loci. We conclude that for ovarian tissue to develop in an XY Thp/+ or XY TOrl/+ individual (1) Tas must be present in a hemizygous state, which is accomplished by heterozygosity for the Thp or TOrl deletions; (2) the AKR/J-derived Y chromosome must be present; and (3) an additional locus involved in primary sex determination must be present in a homozygous C57BL/6J state. This newly identified gene may be one of the previously defined loci, tda-1 or tda-2.

Animals↗
PubMedDate not supplied

Hypervariable yellow (Ahvy), a new murine agouti mutation: Ahvy displays the largest variation in coat color phenotypes of all known agouti alleles.

A new coat color mutation, which occurred spontaneously in the C3H/HeJ strain, has been identified. The original C3H/HeJ male mouse carrying the mutation was unusual because its coat color appeared mostly yellow, in contrast to the wild-type agouti coat normally exhibited by mice of the C3H/HeJ strain. Genetic crosses showed that the mutant phenotype was inherited as a single autosomal dominant gene. The mutation was backcrossed onto a C57BL/6J background and tested for allelism with the agouti locus. The results showed that the mutation, named hypervariable yellow (Ahvy), is a new allele of the agouti locus. Ahvy is unique because mice carrying the mutation can display a range of coat color from pure yellow to almost pure black. The Ahvy mutation is responsible for the largest range of coat color phenotypes yet identified for any single agouti mutation.

Alleles↗